Front Neurosci. 2015 Mar 18; 9: 86. Doi: 10.3389 / fnins.2015.00086. eCollection 2015.
Terbeck S1, Akkus F2, Chesterman LP3, Hasler G2.
inahaneloang
Tlhahlobisong ea hajoale, re fana ka kakaretso ea ho nka karolo ha ts'ebetso ea metabotropic glutamate receptor 5 (mGluR5) le segokanyipalo matšoenyehong a mafu, mathata a maikutlo le ho lemalla. Haholo-holo, re tla hlalosa lithuto tsa mGluR5 ho batho ba sebelisitseng Positron Emission Tomography (PET) mme ba kopanya se fumanoeng le lipatlisiso tsa liphoofolo tsa pele ho nako. Pono ena e kopaneng ea mekhoa e fapaneng ea mekhoa-ho tloha mekhoeng ea mantlha ea methapo ea kutlo ho lithuto tsa batho-e ka fana ka pono e felletseng le e nepahetseng ea bongaka ea ts'ebetso ea mGluR5 bophelong bo botle ba kelello ho feta pono ea data ea pele ho nako. Re tla boela re lekole lintlha tsa hajoale tsa lipatlisiso ho mGluR5 mmoho le Research Domain Criteria (RDoC). Taba ea mantlha, re fumane bopaki ba ts'ebetso e sa tloaelehang ea glutamate e amanang le lits'ebetso tse ntle le tse mpe tsa valence, tse ka fanang ka maikutlo a hore ho kenella ho hanyetsanang le mGluR5 ho na le litlamorao tse khahlano le ho lemalla lithethefatsi, anti-depress le anxiolytic. Taba ea bobeli, ho na le bopaki ba hore mGluR5 e bapala karolo ea bohlokoa lits'ebetsong tsa ts'ebetso ea sechaba le karabelo ea khatello ea maikutlo sechabeng. Kamora nako, karolo ea bohlokoa ea mGluR5 ho homeostasis ea boroko e fana ka maikutlo a hore mokelikeli ona oa glutamate o ka bapala karolo ea bohlokoa ho li-system tsa tsoho le tsa modulatory tsa RDoC. Glutamate pejana e ne e batlisisoa haholo lithutong tseo e seng tsa batho, leha ho le joalo lipatlisiso tsa mantlha tsa bongaka tsa bongaka hona joale li ts'ehetsa khopolo-taba ea hore, ka ho tsekisa ho hlasimoloha ha bokong, methapo ea pelo le ts'ebeliso ea sechaba, ts'ebetso e sa tloaelehang ea metabotropic glutamate e ka beha batho bothateng bo boholo ba mathata a kelello.
Selelekela
Glutamate ke "neurotransmitter" ea mantlha bokong, 'me bafuputsi ba bangata ba khothalelitse hore e bapala karolo ea bohlokoa maemong a fapaneng a bophelo bo botle ba kelello le bongaka. Ho joalo, hangata bafuputsi ba bua ka monyetla oa ho ntšetsa pele phekolo ea meriana ea ionotropic kapa metabotropic bakeng sa mafu a mangata a kelello, ka hore ke a agonists kapa antagonists. Tsebo ka tsamaiso ea glutamatergic e tsoetse pele haholo lilemong tse leshome tse fetileng, tse hlahisitsoeng ke tsoelo-pele ea theknoloji ho li-receptor le transmitter imaging ho batho. Leha ho na le palo e kholo ea lithuto tsa liteko mabapi le ho kenella ha glutamate mathateng a fapaneng a kelello, ho na le khaello ea tlhahlobo e hlophisitsoeng e shebaneng le ho kopanya liphetho tsa lithuto tsa lipatlisiso tsa liphoofolo pele le mekhoa e meng ea neuroscience, joalo ka Positron Emission Tomography (PET) ea batho. . Kahoo, bapisoa le litlhahlobo tse fetileng (Swanson et al., 2005; Pittenger et al., 2006; Kalivas, 2009; Brennan et al., 2012; Luykx et al., 2012; Riaza Bermudo-Soriano et al., 2012), tlhahlobo ena e lekola lithuto tsa batho, haholo lipatlisiso tsa PET, mme e kopanya liphetho tseo le liphetho tsa preclinical.
Positron Emission Tomography (PET)
PET ke mokhoa oa nyutlelie oa bongaka o hlokolosi, o sa tsotelleng, o sebelisang ho hlahisa litšoantšo, ho sebetsana le maemo le ho sebetsa. Ho khetholla li-receptor tsa boko ba motho, ho hlokahala hore ho hlahisoe radio radio receptor ligands (tracers). Sesebelisoa sa scanner se fumana mahlaseli a gamma a kentsoeng ke tracer, e kenngoeng 'meleng. Sehlakahlobu sa mGluR5 PET se loketseng lithuto tsa batho se thehiloe ka katleho Setsing sa Paul Scherrer (PSI) se Villigen, Switzerland le Swiss Federal Institute of Technology (ETH) e Zurich, Switzerland. ABP688 ke mohanyetsi ea se nang tlholisano ebile o khetha haholo, 'me o kopana le sebaka sa allsteric sa mGluR5. 11C-ABP688 e bonts'a khethollo e phahameng bakeng sa mGluR5 le ho phahama ho phahameng libakeng tsa boko tse amohelang li-receptor. Tlhaloso ea pele ea litšobotsi tsena tsa 11C-ABP688 ho liphoofolo e phatlalalitsoe pele (Ametamey et al., 2006). Re bone litholoana tse ts'episang ho tsoa lithutong tse entsoeng ho likhoto tse sebelisang mofuta oa beta ho hakanya kinetics ea tracer ena. Ho feta moo, ha re etsa thuto ea pele ea PET bathong ho lekanya kinetics ho batho (Ametamey et al., 2006) re fumane litholoana tse bapisoang le tse fumanoeng lithutong tsa litekete (Soares le Molao, 2009). Ha joale re sebelisitse tracer e ntlafalitsoeng bakeng sa ho etsa lipatlisiso ka mGluR5 ho baithaopi ba phetseng hantle le bakuli ba kelello. Mekhoa ea PET e fana ka leseli mabapi le botebo ba li-receptor tse sebakeng sa boko tse hlahlojoang. Ha ho na tlhahisoleseling mabapi le khatello ea methapo ea methapo (ke hore, haeba khatello e phahameng ea "receptor" e ka lebisa ho seo e ka bang sesosa sa ketso ea "neurotransmitter") e eketsehang kapa e fokotsoang. Patlisiso ea PET e fana ka tlhaiso-leseling e mabapi le tlhekefetso ea boemo ba receptor ho bakuli ba phelang ba batho mme ka hona e thusa ho lekola hore na ke li-receptors life tse lokelang ho lebisoa ho kalafo ea meriana. Ho fapana le hoo, Magnetic Resonance Spectroscopy (MRS) e fana ka Ka vivo tlhahisoleseling ea biochemical mabapi le lithane tse hlahlojoang (Hasler et al., 2009) ka hona e fana ka leseli mabapi le tekanyo e lekanang ea glutamate metabolite ka lihlopha tsa bakuli. Liphumano tse tsoang liphuputsong tsa PET le MRS li ka hlahisa bopaki bo eketsehileng lithutong tsa liphoofolo tsa pele ho tleliniki. Patlisiso ea liphoofolo ke boemo ba mokhoa oa ho etsa lipatlisiso pele ho litekanyetso. Mefuta e fapaneng ea liphoofolo ea maemo a kelello e se e thehiloe. Lithuto tsa liphoofolo li lumella liteko tsa mechini e lekiloeng, le tlhahlobo ea meriana e mecha mefuteng ena ho fokotsa likotsi tse ka hlahelang batho. Phoso e le 'ngoe bakeng sa lipatlisiso tsa liphoofolo ho mafu a kelello, leha ho le joalo, e ka ba teng tlhahisong ea mehlala e loketseng ea liphoofolo bakeng sa maemo a fapaneng a kelello, ka ho khetheha, maemo a kenyelletsang likarolo tsa kelello tsa motho tsa kahare kapa a ikhethang a ka lebisa mathateng. Kahoo, moriana o mocha oa litlama o bonts'ang ntlafatso ea boitšoaro ba liphoofolo o ka 'na oa se ke oa thusa likarolo tsa kelello tsa motho maemong a kelello.
Pampiri ena e tla hlahloba hore na liphetho tsa lipatlisiso tsa tlhahlobo ea mantlha ea liphoofolo le phuputsong ea kelello ea motho PET li hlahisa pono e lumellanang ea ho nka karolo ha mGluR5 mathateng a kelello. Tlhahlobo ena e tla tšohla feela ts'ebetso ea mGluR5 hobane lintlha tse batsi tsa PET tsa batho li fumaneha ka mofuta ona oa li-receptor. mGluR5 e fana ka sepheo se ts'episang sa nts'etsopele ea lithethefatsi hobane tracer ea PET e ka lekanya mGluR5 e tlamang ho batho, ka hona e fana ka leseli le eketsehileng mabapi le mesebetsi ea eona ho batho. Ka sebele, lipatlisiso li bontšitse hore lithethefatsi tse lebisang sehlopha sa "glabamate" sa "glacam" ke tse ling tsa tse fanang ka tšepiso tse teng tlasa tlhabollo ea kalafo ea mafu a kelello (Krystal et al., 2010).
Thutong ena, re qala ka kenyelletso e khutšoane ea sistimi ea glutamate le mGluR5, ebe re tsoela pele ho lekola ho nka karolo ha mGluR5 mathateng a ho tšoenyeha le mokhoeng, le tšibollo ka ho bapisa liteko tsa preclinical tsa nakong e fetileng le lithuto tsa PET tsa morao-rao. Joale re tla hlalosa mokhoa oa ho nka bohato ba mantlha ba mGluR5 ka ho sebetsa hantle ho kenya letsoho phetohong ea ho ithuta le tšebetso ea sechaba, le ka ho fokotsa thabo maemong a fapaneng a boko.
Sistimi ea Glutamatergic le mGluR5
Glutamate e laola ts'ebetso ea tsamaiso ea methapo e bohareng ka liketso tsa ionotropic le metabotropic receptors. Ho kenya letsoho ha glutamate maemong a fapaneng a kelello le a bongaka ho hlahlojoe ka matla. Leha ho le joalo, mosebetsi oa pejana o ne o shebile haholo li-receptors tsa ionotropic glutamate. Ho fapana le liketso tse potlakileng le tse tobileng tsa li-receptor tsa ionotropic, lihlopha tsena tse tharo tsa metabotropic (mGlu) receptors li fetola tšebetso ea li-neuronal ka ho hlahisa liprotheine tse kopantsoeng tsa G-protein. Lihlopha tsa li-mGluR li khetholloa ke thepa ea tsona ea mahlale le litlhahlobo tse ka hare ho eona. mGluR5, e qalileng ho bopuoa ka liphoofolo ho 1992 mme lilemo tse 'maloa hamorao ho batho, ke karolo ea sehlopha sa I metabotropic receptors (Olive, 2005). Ketso tsa ona di thabisa haholo (Meldrum, 2000). Cleva le Olive (2011) e hlalositse likhokahano tse matla le tšebelisano ea li-receptor lipakeng tsa mGluR5 le NMDA receptor, a fana ka maikutlo a hore mGluR5 le eona e ka ba le tšusumetso e kholo ho hanyetsanang neurality plasticity le lits'ebetsong tsa ho ithuta le tsa memori. Ntle le moo, ho na le bopaki bo bontšang hore ts'ebetso ea mGluR5 e ntlafatsa GABA, haholo-holo ho li-nucleus accumbens (Hoffpauir le Gleason, 2002). Ka hona, ho fanoa ka maikutlo a hore ts'ebetso ea metabotropic glutamate receptor e ka fetola litsela tse nyarosang le tse thibelang (GABA). Tekanyo e phahameng ea mGluR5 receptor e ile ea bonoa haholo literekeng tsa forebrain, striatum, le libaka tse maoto le matsoho ho kenyelletsa amygdala le hippocampus (Swanson et al., 2005). U sebelisa mekhoa e tsoetseng pele ea baeloji ea limolek'hule ho khetholla polelo ea mGluR5 mRNA bokong ba methapo, patlisiso e fumane hore libaka tsa bulb ea ophodoal, dorsal striatum, li-nucleus tsa li-lateral septum, le hippocampus li bonts'a maemo a holimo haholo a polelo ea mGluR5 (Abe et al., 1992) (Bona setšoantšo 1).
Tšoantšiso 1
Setšoantšo sa 1. Localization of mGluR5 mRNA in the older and the 6-day-rat rat tsa kelello ka in situ nyallelloa. Litšoantšo tse mpe tsa filimi ea "sagittal" ea karolo ea bongoana ea "rat rat" (A) le boko ba matsatsi a 6 ba letsatsi la khale (B) lia bontšoa. OB, konokono ea sehlooho ea olgicory; Ac, li-nucleben tsa bokellane; Tu, tubercle ea olildory; St, striatum; Hi, hippocampus; S, subiculum; Cx, cortex ea qoqotho; LS, lateral septal nucleus; IC, colliculus e tlaasana; Cb, cerebellar cortex; Sp, lesapo la mokokotlo la lesapo la mokokotlo; T, thalamus; VMH, nucleomyedial hypothalamic nucleus. Mokotla oa sekala, 4 mm. Ho tloha Abe et al. (1992). Tlhokomeliso: palo le nalane ea eona e hlahisoa hape ka tumello.
Li-receptors tsa pre-synaptic mGluR5 li fumanoe li nka karolo ho laoleng taolo ea polasetiki ea synaptic le liphetoho ho thabo ea neuronal ho boloka homeostasis (Schoepp, 2001). Habohlokoa, polelo ea bohlokoa ea mGluR5 e se e kanngoe ho 9 Gestational Week (GW) prenatal (Boer et al., 2010). Ho ekelletsa moo, polelo ea mGluR5 e fumanoe e phahame haholo ho liphoofolo tse nyane ho feta ho batho ba baholo (Romano et al., 1996), ho fana ka tlhahiso ea hore ho kenella pele ho lebisang mGluR5 ho kanna ha ba le litlamorao ho ts'enyehelo ea methapo ea methapo.
Ka lebaka la ts'ebetso ea eona lits'ebetsong tse fapaneng tsa neuronal, ho senyeha ho hoholo tsamaisong ea glutamate ho lebisa ho senyeha ho matla ha methapo (mohlala, ho tsietsana), athe liphetoho tse nyane li ka kenya letsoho maemong a fapaneng a kelello (Yüksel le Öngür, 2010). Boiteko ba ho nts'etsapele lithethefatsi tse ikemiselitseng mGluR5 e qalile matsatsing a 90. Ho fihla joale, li-agonists tse fapaneng tsa mGluR5 le antagonists li se li hlahisitsoe (Bona Lea le Faden, 2006 bakeng sa leseli le eketsehileng mabapi le nts'etsopele e khethehileng ea lithethefatsi). Mohlala, 3- [2-methyl-1,3-thiazol-4yl] ethynyl] pyridine (MTEP) ke mohanyetsi ea ikhethileng haholo ea bileng a se nang tlholisano ea mGluR5 h ea kenang molek'hule ka botlalo ea 1 h kamora ho kenngoa ka ente ka likhoto tsa 10 h mg / kg (Anderson et al., 2003). Tafole 1 e fana ka kakaretso ea lithethefatsi tse ling tsa mGluR5 tse sebelisitsoeng ho liphoofolo le tse neng li sebelisoa pele litekong tsa pele tsa bongaka ba batho.
TABLE 1
Lethathamo la 1. Khetho ea mGluR5 litlhare tse sebetsang tsa meriana.
Bofokoli ba kelello le tlholeho e ipapisitseng le batho ba bang
Mathata a kelello a mangata haholo 'me' mele o lula o kopane 'meleng. Leha ho le joalo, liphekolo tse tloaelehileng tsa kalafo ea meriana ea mafu a kelello li thehiloe ho mekhoa e fokolang ea pathophysiological, ka mohlala, ho eketsa ho fumaneha ha monoamine ka matšoenyeho le khatello ea maikutlo. Kahoo, ho na le tlhoko e potlakileng ea ho ntlafatsa le ho ntšetsa pele liphekolo tsa mafu a kelello, mme ho kenella hoa meriana litabeng tsa metabotropic ke tsoelo-pele e tšepisang ntlheng ena (Agid et al., 2007).
Liteko tse ngata tsa batho li entsoe linyeoeng tsa Fragile X Syndrome (FXS). Khopolo ea mGluR5 ea FXS e tiisa hore ho haella ha protheine ea kelello ea kelello ea reteleha X (FMRP) ho fella ka ho hlahisa signutamatergic ho feteletseng ka mGluR5 (Bear et al., 2004). Sena se lebisa ho phetolelo ea lehae ea mRNA sebakeng sa synapse hobane FMRP ha e teng ho laola ts'ebetso. Qetellong, sena se fokolisa ho nyefola le ho baka palo e eketsehang ea methapo ea methapo e sa sebetseng, e ka hlalosang ho holofala ha mahlale a fumanoang ho bakuli ba FXS. Bokowa bona bo amahanngwa le matshwao a ho feto-fetoha ha maikutlo le ho tšoenyeha 'me hangata bo ba teng ka lintho tse atileng bothateng ba Autism spectrum disorder, ho kenyelletsa ho lieha ho ntlafatso ea puo le puo, maikutlo a senyehileng a kelello, le ts'ebetso e mpe ea maemo a bophelo le maikutlo, hammoho le boits'oaro bo pheta-phetoang (Garber et al., 2008). Bopaki ba pele le bo sa tobang ba hore mGluR5 antagonist e ka ntlafatsa botsoalle ho FXS (Burket et al., 2014) e phahamisa ts'epo ea hore lithethefatsi tse lebisang mGluR5 e kanna ea ba tsa ts'ebeliso ea bongaka maemong a atileng a kelello a amanang le litsamaiso tse sitisang lits'ebetso tsa maemo a bophelo tse kang autism, schizophrenia, le khatello ea maikutlo. Ntle le moo, mokhoa o shebahalang oa ho pheta-pheta o ka bonoang ho FXS o ka fana ka tlhahiso ea hore ho na le karohano e arolelanoang ea mafu a kelello har'a mafu a mang a mafu a kelello joalo ka ho senyeha ha kelello (OCD) le ho lemalla.
Leha ho bile le keketseho tsebong ea mahlale le lipatlisiso ka mGluR5, boiteko ba nts'etsopele ea lithethefatsi ha bo atlehe (Agid et al., 2007). Lithethefatsi tse lebisang li-receptor tsa ionotropic hangata li hlahisa litlamorao tse ngata mme maano a hona joale a nts'etsopele ea lithethefatsi ha a so hlahise litheko tse khethiloeng bakeng sa li-receptor tsa ionotropic tse ka fokotsang litlamorao tse mpe. Mohlala, bahanyetsi ba ionotropic receptor ba hlahisa litla-morao ho batho tse kenyeletsang ho senyeha hoa memori, liketsahalo tsa kelello le lichapo (Swanson et al., 2005). Litlamorao tse mpe li ka hlaha hobane li-receptor tsa ionotropic glutamate li na le phetisetso e ntle, athe li-receptor tsa metabotropic li sa lekane ebile li ajoa ka mokhoa o khethang (Krystal et al., 2010). Ka lebaka leo, nts'etsopele ea morao-rao ea lithethefatsi e shebile haholo ho likhomphutha tse lebisang li-metabotropic receptors ho nka hore lithethefatsi tse joalo li tla amahanngoa le litlamorao tse fokolang ho feta tse tlamahanang le li-receptor tse sebetsang ka potlako tsa ionotropic.
Likarolong tse latelang, re tla hlahloba bopaki bo tsoang ho lithuto tsa PET tsa batho mabapi le ho nka karolo ha mGluR5 mathateng a maikutlo le ho lemalla le ho bapisa seo ba se fumaneng le lithuto tsa liphoofolo. Ho feta moo, re tla hlalosa libaka tse ling tsa boko bakeng sa ts'ebetso ea mGluR5 ho batho mme qetellong re fane ka tlhahiso ea hore na ts'ebetso ea mGluR5 e tobileng le e sa tobang e ka kenya letsoho joang litabeng tsa kelello tsa batho.
mGluR5, Matšoenyeho a Pathological, le Mathata a Mood
Matšoenyeho a Kelello
Matšoenyeho a lefu la kelello a hlaha mathateng a ho tšoenyeha, ho kenyelletsa ho tšoenyeha ka kakaretso, ho tšoha ka letsoalo (maemo a kelello a atileng haholo lefats'eng ka bophara, Pele le Gibbon, 1997), empa hape le maemong a mang a atileng a kelello a kang ho tepella maikutlo le khatello ea kelello e hlokisang botsitso (OCD). Maemo ana a kelello a baka ho senyeha ho hoholo mosebetsing le mesebetsing, ho lebisang meroalo ea litšenyehelo tsa bophelo bo botle le mahlomola a mokuli (Pele le Gibbon, 1997). Ka kakaretso, matšoenyeho a ka 'na a amahanngoa le thabo e fetisisang ea boko (Harvey le Shahid, 2012).
Patlisiso ea Previrinical Neurobiological
Liphumano tse tsoang lipalo tse ngata tsa liteko tsa liphoofolo tse khethiloeng esale pele li bonts'a phello ea kalafo ea merafo ea mGluR5 ka matšoenyeho. Swanson et al. (2005) e lekola lithuto tsa liphoofolo ka lithethefatsi tse lebisang mGluR5 ho boits'oaro bo joalo ba ho tšoenyeha. Ba ile ba fihlela qeto ea hore kalafo ea ho hanyetsa ka mokhoa oa mGluR5 hangata e lebisa ho likarabo tse tšoenyang ho liphoofolo tse lekang. Haholo-holo, litlamorao tse kang ho fokotseha hoa maemo a ho bata, ho ts'oaroa le ho amoheloa ha kotlo, le ts'ebelisano e kholo li ile tsa bonoa. Mohlala, tekanyetso e le 'ngoe ea 2-methyl-6- (phenylethynyl) pyridine (MPEP) e ekelitse nako ea likhoto tse sebelisitsoeng letsohong le bulehileng la ts'ebetso ea liteko, ntle le ho ama ho hlophisa kapa boits'oaro ba motor (Tatarczyńska et al., 2001). Krystal et al. (2010) e hlahlobe lithuto tsa preclinical tsa liphoofolo tse ileng tsa hlahloba bahanyetsi ba mGluR5 (MTEP, MPEP, fenobam) mefuteng ea mouse ea matšoenyeho. Lithuto tsena li sebelisitse mehato e fapaneng ea sephetho, joalo ka ho felisoa ha boemo ba tšabo le likarabo mohloling o mong o phahameng, ho lekola katleho ea kalafo ea lithethefatsi. Ho lithuto tse hlahlojoang, 88.45% e tlalehile phello ea ho tšoenyeha le bahanyetsi ba mGluR5 (Krystal et al., 2010). Haufinyane tjena, tekolo e 'ngoe mabapi le lipatlisiso tsa matšoenyeho mefuteng ea liphoofolo e ileng ea lekola phello ea ho kenella ha ionotropic le metabotropic glutamate receptor antagonist e phatlalalitsoe (Riaza Bermudo-Soriano et al., 2012). Mabapi le mGluR5, bangoli ba thathamisitse lithuto tsa liphoofolo tsa 43 tsa matšoenyeho, 'me kaofela ntle le tse peli li bontšitse litlamorao tse tšoenyang.
Lithuto tsa Batho
Bopaki ba pele ba khopolo ea hore ts'ebetso ea glutamate ha e sebetse mathateng a ho tšoenyeha e tsoa lipatlisisong tsa MRS. Mohlala, ba sebelisa sebopeho sa maqhubu a maqhubu a 1H se nang le voxel e phahameng, bafuputsi ba fumane hore ha ho bapisoa le taolo e phetseng hantle, bakuli ba nang le bothata ba ho tšoenyeha ka maemo a sechaba ba bontšitse maemo a phahameng haholo a "cortex cortex" ea Aterior.Phan et al., 2005). Ho feta moo, lipatlisiso li fumane ho eketseha ha khatello ea glutamate ea lefatše ho bakuli ba 10 ba nang le phobia ea sechaba (Pollack et al., 2008). Joalokaha ho boletsoe pejana, lithuto tsena, leha ho le joalo, li ne li sa khone ho fumana hore na li-receptors tsa glutamate li amanang le ts'ebetso e feteletseng ea glutamate e ne e le eng.
Re sebelisa mokhoa oa ho etsa lipatlisiso oa PET, haufinyane re bile ba pele ba ho bonts'a likamano lipakeng tsa mGluR5 le matšoenyeho, ho Major Depression Disorder (MDD), le OCD. Phuputsong e le 'ngoe, re entse lipatlisiso tsa mGluR5 Distribution Volume Ratio (DVR) ho bakuli ba 10 ba nang le OCD le 10 taolo e phetseng hantle ba sebelisa [11C] ABP688 PET (Akkus et al., 2014). Re sebelisitse Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) e le tekanyo ea bongaka ea matšoao a OCD. Re hlokometse khokahano ea bohlokoa lipakeng tsa marang-rang a Y-BOCS a ho itlhahisa ka bongata le mGluR5 DVR libakeng tsa amygdala, ACC, le medial orbitofrontal cortex (Akkus et al., 2014). Libaka tsena tsa boko li kile tsa ba le tšusumetso ho OCD pathophysiology. Haele hantle, tlhekefetso ea popelo bokong ho amygdala, ACC le orbitofrontal cortex ka mokhoa o ts'oanang li amahantsoe le OCD (Rosenberg le Keshavan, 1998; Szeszko et al., 2008; Van den Heuvel et al., 2009). Ha ho fanoa ka hore lithuto tsa sebopeho sa monahano li fane ka bopaki ba khokahano e ntle pakeng tsa ho teba ha OCD le bophahamo ba litaba tsa bohlooho (Zarei et al., 2011), ho eketseha ha mGluR5 ho OCD ho ka bontša letsoalo le eketsehang la li-neuron. Leha ho DSM-5 OCD ha e sa nkoa e le bothata ba ho tšoenyeha, bakuli ba OCD ba bangata ba na le matšoao a ho tšoenyeha. Mohlaleng o moholo oa tleliniki, re kile ra supa hore bakuli ba OCD ba nang le ts'oaetso ba na le ts'oaetso e phahameng haholo ea matšoao a ho tšoenyeha le mathata (Hasler et al., 2005). Pampiring ena, re khothalelitse hore maikutlo a kenyelletsang khatello ea maikutlo, matšoenyeho, kapa likhohlano a ka amahanngoa le ho eketseha ha glutamatergic neurotransmission ho amygdala, ACC, le orbitofrontal cortex.
Ha ho kopanngoa hammoho, liphumano tse tsoang lipatlisisong tsa morao-rao tse sebelisang mekhoa e fapaneng ea ho etsa lipatlisiso li ts'ehetsa maikutlo a hore ts'ebetso ea glutamate ha e tloaelehe libakeng tsa bohlokoa tsa tsamaiso ea maoto le methapo ea maikutlo e amanang le ho tšoenyeha. Ts'ebetso e sa tloaelehang e ka boela ea amana le receptor ea mGluR5. Kaha, pele ho tleliniki, le lipatlisiso tsa PET li bonts'itse mokhoa o lumellanang oa sephetho, re fana ka maikutlo a hore kalafo ea mGluR5 e ts'oarehang e ka hlahisa litlamorao tse kholo tsa bakuli ba nang le matšoenyeho a pathological.
Mathata a maholo a khatello ea maikutlo (MDD)
Patlisiso ea Previrinical Neurobiological
Thutong ea bona, Krystal et al. (2010) o hlalositse sephetho sa lithuto tse robeli tse batlisisang mGluR5 antagonists MTEP le MPEP mefuteng ea liphoofolo ea khatello ea maikutlo. Ha ho bapisoa le litekanyetso tsa katleho ea kalafo bakeng sa mathata a ho tšoenyeha, bangoli ba tlaleha hore ke 62.5-75% feela e fumaneng phello e hlakileng ea antidepressant, leha kalafo e sebelisitsoe le ionotropic NMDA ketagonist ketamine e bontšitsoe ho lebisa litlamorao tse potlakileng tsa kalafo, esita le ho bakuli ba hanyetsang kalafo.Pittenger et al., 2006).
Lithuto tsa Batho
Tlhahlobo ea morao-rao e hlahlobe lithuto tsa 13 MRS tsa mathata a maikutlo. Bangoli ba tlaleha hore lithuto tsena li lula li fumana bopaki ba hore glutamate e fokotsehile ho MDD (Hasler et al., 2007; Yüksel le Öngür, 2010). Haholo-holo, litekanyetso tse fokotsang tsa glutamate ho ACC, li-cortex tsa dorsolateral pele pele, corsex ea dorsomedial pre mapemaal, cortex ea ventromedial prewardal precyal, amygdala, le hippocampus. Tlhahlobo ea morao-rao mabapi le lithuto tse sebelisang MRS ho hlahloba glutamate ho MDD e tiisitse hore khatello ea glutamate ho ACC e fokotsehile kamehla (Luykx et al., 2012). Ka occipital cortex, glutamate e eketsehileng e fumanoe ke bafuputsi ba bang, ba neng ba le kaholimo ho sehlopha sa bakuli ba MDD (se phahameng ka ho fetisisa sa melancholic).Sanacora et al., 2008).
Phuputsong e fetileng, re fumane litšoantšo tsa PET tsa mGluR5 receptor e tlamang lithutong tse sa ngolisoang tsa 11 tse nang le li -DD le li-11 li-control tsa bophelo bo botle (Deschwanden et al., 2011). Re fumane ho fokotseha ha tikoloho ea mGluR5 e tlamang ka cortex ea pele, cingrate cortex, insula, thalamus, le hippocampus ea bakuli ba nang le khatello ea maikutlo. Ntle le moo, botebo ba khatello ea maikutlo bo amanang le mGluR5 e tlamang hippocampus. Re khothalelitse hore liphumano tsena li bonts'e li-neurotransication tse fokotsehileng tsa mGluR5 ho tepelletseng maikutlong, mohlomong ka lebaka la liphetoho tsa basal kapa tse tlatselletsang ts'ebetsong ea tsamaiso ea glutamate. Ntle le moo, re ile ra hlahloba palo ea polelo ea mGluR5 ho li-sampuli tsa boko ba post-mortem tsa lithuto tse sithabetseng tsa 15 le li-taolo tse tšoanang tsa 15 (Deschwanden et al., 2011). Re bone ho fokotseha ha polelo ea mGluR5 ho preortal ea cortex ho mehlala e fumanoeng ho batho ba tepelletseng maikutlo. Polelo ea receptor e fokotsitsoeng ea NMDA bokong ba kamora lefu-lefu la bakuli ba tepelletseng le eona e tlalehiloe (Feyissa et al., 2009). Kannete, ho kile ha etsoa tlhahiso ea hore litheko tsa antidepressant tsa mGluR5 antagonists li ka kenyelletsa ho thibeloa ha li-receptor tsa NMDA. Sena se ka 'na sa sebetsa pakeng tsa methapo ea kutlo le / kapa ho kenyelletsa polelo ea tlhaho ea neurotropic factor ka hippocampus (Legutko et al., 2006). Ho feta moo, phuputso ea morao-rao e bontšitse hore ho hloka boroko ho eketsa ho fumaneha ha mGluR5 ho batho ba phetseng hantle (Hefti et al., 2013). K'homphieutheng ea anterior cingulate cortex, insula, medial tempobe lobe, parahippocampal gyrus, striatum le amygdala, keketseho ena e hokahane haholo le katleho ea boroko ba boroko joalo ka ha e bontšoa ke boroko bo eketsehileng bo ikhethileng. Phuputso ena e fana ka maikutlo a hore keketseho ea mGluR5 e kanna ea ba sesebelisoa sa methapo ea kutlo se hlalosang ts'ebeliso e ntle ea khatello ea boroko. Liphuputso tse entsoeng esale pele li tiisa kamano ea rona e ikemiselitseng lipakeng tsa mGluR5, boroko le khatello ea maikutlo. Haholo-holo, phuputso e entsoeng ho litoeba tsa mGluR5 e fana ka bopaki ba bohlokoa ba hore mGluR5 e kentse letsoho ho theheng botsitso ba maemo a boroko a NREM a ho robala-REM, ts'ebetso ea NREM butle-butle le karabelo ea homeostatic ho lahleheloeng ke boroko (Ahnaou et al., 2015).
Ho akaretsa, ho na le bopaki bo fetohang bo tsoang liphuputsong tsa liphoofolo, postmortem, MRS, le PET tsa hore sisteme ea "glutamate" e bohlokoa e kentse letsoho ho pathophysiology ea MDD. Leha ho le joalo, bopaki bo fana ka maikutlo a hore ho qhekella ha mGluR5 ho ka 'na ha se ke ha thusa ka ho toba bakuli ba nang le MDD. Sena se tsamaisana le ho fumana ha rona polelo e fokotsitsoeng ea mGluR5 ho bakuli ba MDD. Ho ka nahanoa hore lithethefatsi tse shebileng sisteme ea mGluR5 li ka ba molemo haholo ho bakuli ba sithabetseng ba nang le matšoenyeho a comorbid, mathata a ho lemalla le / kapa lithothokiso tse potileng tsa circadian. Ho feta moo, mathata a teng litsing tsa lits'ebetso tsa maemo a bophelo a tloaelane le MDD. Tsebo e fokolang ea sechaba e bonahala e le karolo ea bohlokoa ea kotsi ea khatello ea maikutlo (Segrin, 2000). Liphoso tse joalo li kenyeletsa boits'oaro ba puo le lipuo, le litšitiso ponahalong ea sefahleho, mahlo, boemo le boitšisinyo, tse ka bapisoang le tse bonoang ho FXS le autism spectrum disorder. Ntle le moo, malebana le litsebo tsa maemo a bophelo, liteko tsa litoeba tse pepesitsoeng khatello ea maikutlo ea sechaba li bonts'itse hore Homer1 / mGluR5 coupling e sitisitsoe, ho fana ka maikutlo a hore bosiu ba mGluR5 bo leka ka matla ho hlaseloa habonolo ha khatello ea maikutlo sechabeng (Wagner et al., Ka khatiso). Ntle le moo, mehlaleng ea litoeba tsa bofokoli ba sechaba, khatello ea mGluR5 e lebisitse ho tloaelano ea litšebelisano tsa sechaba (Chung et al., 2015). Ka bobeli, lithuto tsena li fana ka bopaki ba pele ba hore mGluR5 e bapala likarolo tsa bohlokoa lisosa tsa bophelo ba khatello ea maikutlo le bofokoli ba sechaba bo atisang ho hlokomeloa hangata ho bakuli ba tepelletseng maikutlo. Ka lebaka leo, lithethefatsi tse lebisang mGluR5 li ka bapala karolo ea bohlokoa ho thibela nts'etsopele ea khatello ea maikutlo ho bacha ba nang le bofokoli ba sechaba mme e ka thusa ho phekola bofokoli ba sechaba le ts'ebetso e tlase ea kelello ho bakuli ba MDD.
mGluR5 le Tlatsetso
Ho lemalla ho bonahatsa tšebeliso ea lithethefatsi tse tsoelang pele le ha ho bile le litlamorao tse mpe, liteko tse sa atleheng khafetsa tsa ho emisa kapa ho fokotsa tšebeliso ea lithethefatsi, le matšoao a ho mamella le ho tlohela. Le ha tsamaiso ea dopamine e bapala karolo ea bohlokoa ts'ebetsong ea moputso o matla (Kalivas le Volkow, 2005), ho na le bopaki bo ntseng bo eketseha bo tlatselletsang glutamatergic neurotransication tlatsong (Krystal et al., 2010).
Patlisiso ea Previrinical Neurobiological
Ho 2001, thuto ea seminal ho mGluR5 le papatso li phatlalalitsoe (Chiamulera et al., 2001). Bangoli ba bontšitse hore litoeba tse haelloang ke li-receptor tsa mGluR5 li ile tsa sitoa ho ipata kahare ho sa le ho bonts'a litekanyetso tse eketsehileng tsa extracellular dopamine ka har'a li-nucleus tse latelang kamora ho kenella ka bongata. Liphuputso tse ngata tsa ho latela liphoofolo li bontšitse hore mGluR5 receptor antagonists MPEP le MTEP li fokotsa ho itaola ha lithethefatsi tse lemalloang tse kang cocaine le nikotine (Kalivas, 2009). Olive (2005) e ile ea lekola lithuto tsa liphoofolo tse amanang le tšebeliso ea lithethefatsi 'me ea khothaletsa hore ho na le bopaki ba hore mGluR5 e ka ameha nts'etsopele, ho bona moputso le ho khutlisetsa tšebeliso ea lithethefatsi joalo ka cocaine, morphine, nikotine le ethanol. Bangoli ba hlalositse bopaki bo tsoang liphuputsong tsa liphoofolo hore menahano ea mGluR5 e fokotsa boikemelo ba lithethefatsi, le boitšoaro bo latelang ba ho batla lithethefatsi. Mohlala, haufinyane tjena, ho ile ha fumaneha mofuta oa mofuta oa mofuta oa bothateng ba ho ja lijo tse bobebe hoo MTEP e ileng ea fokotsa tšebeliso ea lipompong ntle le ho fetola boits'oaro ba ho batla lipompong (Bisaga et al., 2008). Patlisiso e khothalelitse hore ho fokotseha ha tšebeliso ea lijo tse amanang le tšebeliso ea litheko tsa mGluR5 receptor ho ka amana le phokotso ea boleng bo putsa ba khothatso e matlafatsang (Bisaga et al., 2008). Ntle le moo, lipatlisiso li tlaleha keketseho e kholo ea maemo a mGluR5 mRNA ho li-bokellane tsa nucleus le dorsolateral striatum kamora ho phetoa khafetsa ha koae ho litoeba tsa liteko (Bisaga et al., 2008).
Lithuto tsa Batho
U sebelisa li-autoradiography ho li-sampole tsa boko tsa post-mortem tse fumanoeng ho bakuli ba nang le mathata a joala le taolo e phetseng hantle, patlisiso e fumane 30-40% e phahameng mGluR1 / 5 e tlamang letsoalo ho hippocampus le striatum ho bakuli ba nang le mathata a joala (Kupila et al., 2012). Seo ba se fumaneng se bonts'itse hore mGluR5 receptor density e kanna ea eketseha libakeng tse ling tsa boko ba bakuli ba lemaletseng joala. Haufinyane tjena re sebelisitse PET ho lekanya li-receptor tsa mGluR5 bokong ba batho ba nang le lithethefatsi tsa nikotine (Akkus et al., 2013). Re fumane phokotseho ea lefats'e ea mGluR5 DVR litabeng ea bohlooho ea batho ba tsubang ba 14 ha ba bapisoa le batho ba sa tsubang (Bona setšoantšo. 2). Phokotso e hlahelletseng e fumanoe ka letsohong le letona le ka ho le letšehali la medial orbitofrontal cortex. Re khothalelitse ho fokotseha hona ha li-receptor tsa mGluR5 e ka ba phetoho ea nako e telele ea ho eketseha ho sa feleng ha glutamate e susumetsoang ke tsamaiso ea nicotine e sa foleng. Tloaelo ena e bonahala e khethehile ts'ebeliso ea nicotine kaha e sa fumanehe ho basebelisi ba koae ba sa tsubeng.Hulka et al., 2014).
Tšoantšiso 2
Setšoantšo sa 2. Setšoantšo se bonts'a bokaholimo bo akaretsang ba mGluR5 DVR ka lihlopha tse tharo tsa tlhahlobo. Ho bokelloa ha kelello ho bonahala ho fokotsehile ka lihlopha tsa batho ba tsubang le ba tsubang. Litšoantšo li baloa ke mofuta oa software ea PMOD 3 (PMOD Technologies). Ho tloha Akkus et al. (2013). Tlhokomeliso: palo le nalane ea eona e hlahisoa hape ka tumello.
Ho hlile ho khothalelitsoe hore mGluR5 downregulation e emetse neuroadaptation e tlatselletsang (Kalivas, 2009), khothalletso ea moputso o susumetsoang ke lithethefatsi (Rutten et al., 2011), kapa ntho e kopanyang litlamorao tsa litaba tse amanang le maemo a arabeloang ka tsela e hlophisitsoeng (Tronci et al., 2010). Setšoantšo 3 e hlahisa mokhoa oa ho se sebetse hantle oa mGluR5 ho lemeng.
Tšoantšiso 3
Setšoantšo sa 3. ho nka karolo mGluR5 ho lemalla.
Joalokaha ho bonoa ho Setšoantšo 3, patlisiso e fetileng e ts'ehetsa mohopolo oa hore mGluR5 e kenya letsoho mehatong e meraro ea bohlokoa ea ho lemalla, ho nts'etsopele le ho fumana thepa, ka boleng ba matlafatso ea lithethefatsi, hammoho le ho oela hape ts'ebelisong. Ho kanna ha etsoa tlhahiso ea hore ts'ebetso e 'ngoe le e' ngoe e hlalosoa ka nepo ke libaka tse fapaneng tsa boko, tse bonts'ang maemo a phahameng a mGluR5 receptor density, mme tse bonts'itsoeng li bonts'a khatello ea methapo ea MGluR5 lipatlisiso tsa rona tsa PET (Deschwanden et al., 2011). Kalivas (2009) o qapile mokhoa o pharaletseng oa bokhoba ba ho lemalla. Sengoli se bontšitse hore ho lemalla ho tsamaisana le ho se sebetse hantle maemong a bohlokoa a potoloho ea boko ea corticostriatal, ho kenyelletsa amygdala, nucleus accumbens (NA), cortex ea pele le motor. Joalokaha re khothaletsa ho Setšoantšo 3, pele ("Karolo e susumetsang"), "cortex ea pele" e ka ba moeli le tšusumetso ea kelello nakong ea methati ea pele ea tlhabollo ea lithethefatsi. Boithuto ba pele-pele ke Chiamulera et al. (2001) e fana ka maikutlo a hore mGluR5 ea hlokahala mohatong ona oa ntlafatso ea bokhoba ka ho kena-kenana le litheko tse ntle tsa lithethefatsi tsa tlhekefetso. Bobeli ("Karolo ea moputso"), Nucleus Accumbens (NA) e bontšitsoe ho susumetsa boleng bo khotsofatsang ba moriana, eseng feela ka dopamine empa hape le ka mosebetsi oa mGluR5 (Bisaga et al., 2008). Ka ho khetheha, ho senyeha ha phetiso ea glutamate lipakeng tsa prelimbic cortex le NA ho fanoe ka maikutlo a hore ho batla lithethefatsi ho thehiloe ka ts'epo e kholo ho boits'oaro bo ithutileng bo amanang le NMDA / mGluR5 receptor system (Kalivas, 2009). Khetlo la boraro ("Karolo e Batlang Bongaka"), lipatlisiso tse ling li ts'ehetsa hore mGluR5 e ameha ho ts'epahalong e kholo ea ts'ebetso ea makoloi - ho fokotsa taolo ea kelello - ka striatum (Kupila et al., 2012). Patlisiso ea rona e phatlalalitsoeng le e sa phatlalatsoang e fana ka maikutlo a hore ho fokotseha ha mGluR5 ho amana le kotsi e eketsehang ea ho khutla ho batho ba tsubang (Akkus, PNAS). Phokotso eo e ka ba pathogenic kapa phetoho e sa lekaneng ea matšeliso. Ha ho kopantsoe hammoho, patlisiso ea morao-rao e bonts'a hore lithethefatsi tse lebisitsoeng mGluR5 li ka ntlafatsa kalafo ea mathata a bokhoba ba methati mefuteng e fapaneng ea kholo ea bona.
Puisano
Bopaki bo shebiloeng bo fana ka maikutlo a ho nka karolo e phahameng ea mGluR5 ka har'a mathata a ho tšoenyeha, OCD, MDD, hammoho le ts'ebetso ea lithethefatsi, le hore kalafo ka mGluRXNNXX e tsebisoang litlhare tsa meriana e ka ba molemo ho batho. Leha ho le joalo, pathožisis ea maikutlo le matšoao a ho tšoenyeha a amanang le OCD e ka fapana le matšoao a ho feto-fetoha le matšoao a ho tšoenyeha a sa amaneng le OCD. Ka lebaka leo, boteng ba matšoao a bonoang ka mokhoa o bonts'ang maikutlo e kanna ea ba ponelopele ea karabelo e potlakileng le e tšoenyang ho lithethefatsi tse lebisitsoeng mGluR5. Ho feta moo, re khothalelitse hore lithethefatsi tse shebileng sisteme ea mGluR5 li ka thusa ho eketsa ho hanyetsa khatello ea maikutlo le ho ntlafatsa likhaello tsa sechaba maemong a khatello ea maikutlo. Kaha khatello ea kahisano ke eona ntho ea bohlokoahali eo e seng ea liphatsa tsa lefutso e bakang khatello ea maikutlo le bofokoli ba sechaba bo hokahane haufi le phokotso ts'ebetsong ea sechaba le boleng ba bophelo, liphetho tsena lipatlisisong tsa liphoofolo li na le bohlokoa bo holimo saenseng le tleliniking.
Haufinyane, National Institute of Mental Health (NIMH) e thehile buka ea nalane, e mabapi le projeke ea thekiso: The Domain Criteria (RDoC). Sena se bonts'oa ts'ebetsong ea NIMH Strategy 1.4 "Ho nts'etsopele sepheo sa ho etsa lipatlisiso, mekhoa e mecha ea ho khetholla mafu a kelello a ipapisitse le maemo a bonoang a boitšoaro le methapo ea kutlo." (http://www.nimh.nih.gov/research-priorities/strategic-objectives/strategic-objective-1.shtml). Bohato bona e bile litholoana tsa ho hlophisa mekhahlelo e thata ea DSM, eo boholo ba eona e ileng ea ntlafatsoa le pele ho lipatlisiso tsa neuroscience (Morris le Cuthbert, 2012). RDoC e hlalosa libaka tse hlano kapa liemahale; Sistimi e mpe ea valence, Sisteme e ntle ea valence, Sistimi ea Cognitive, Sisteme ea lits'ebetso tsa sechaba, lits'ebetso tsa Arousal / taolo. Ho latela bopaki bo shebiloeng mabapi le ho ba le seabo ha mGluR5 ho MDD le OCD, re fana ka tlhahiso ea hore ts'ebetso ea mGluR5 ka kotloloho e amanang le ts'ebetso e mpe ea valence, e kenyelletsang lintlha tse bonts'itsoeng tsa tšabo, ts'oso, ts'okelo e tsitsitseng, tahlehelo, le pherekano e seng. moputso. Kahoo, joalo ka ha lithuto tse hlahlojoang li bontša, kalafo e hanyetsanang le mGluR5 e lokela ho fokotsa matšoao a bonoang. Ntle le moo, re fana ka maikutlo a hore kalafo ea mGluR5 e ka ba molemo ho "mathata a valence" a joalo ka bokhoba le khatello ea maikutlo ka ts'ebetso e sa tloaelehang ea mGluR5 mabapi le sebopeho sa boko le ts'ebetso e amanang le glutamatergic NMDA receptor e amanang le mGluR5 mme e bohlokoa ho kenya letsoho ho ithuteng moputso. . Ka mohlala, Simonyi et al. (2010) e ile ea lekola lithuto tse ngata tsa liphoofolo tse sebelisitseng lisele tsa mGluR5 ho li-knockout ho tseba karolo ea mGluR5 ho ithuta le ho hopola. Ho ithuta ka inhibitory, joalo ka ho ithuta ho qoba ho ithuta, ke mosebetsi o thehiloeng hantle mehlaleng ea liphoofolo o sebelisoang ho ithuta mekhoa ea ho ithuta ea hippocampal, mme o bontšitsoe lithutong tse ngata ho its'etleha holima mGluR5 receptor (Simonyi et al., 2010). Mohlala, lipatlisiso li bonts'itse hyperexpression ea protheine ea mGluR5 ho CA3 nakong ea nako e khuts'oanyane le CA1 nako e telele ea ts'ebeliso ea likhoto (Riedel et al., 2000). Hyman (2005) e hlahisitse mofuta oa tlhaho oa ho lemalla o kenyelletsang mekhoa e sa tloaelehang ea ho ithuta le ho hopola e etsang lintho tsa motheo tsa ho lemalla. Bangoli ba hlahisitse tlhahiso ea tšohanyetso ea nako e telele, e kenyeletsang, liphetoho lipakeng tsa li-receptor tsa glutamate, le taolo ea polelo ea liphatsa tsa lefutso e le mekhoa ea bohlokoa bakeng sa liphetoho tse bakoang ke lithethefatsi tse fumanehang makaleng a sa tloaelehang a amanang le tšebeliso ea lithethefatsi. Kamora nako, lithuto tsa mGluR5 le homeostasis ea ho robala (Hefti et al., 2013; Ahnaou et al., 2015) fana ka maikutlo a karolo ea bohlokoa ea mGluR5 ho li-system tsa tsoho le li-modulatory tsa RDoC.
Figure 4 e akaretsa mekgwa e reriloeng ho buella liketso tsa mGluR5 mathateng a maikutlo le bokhoba ba tahi. Bokaholimo ba Setšoantšo 4 e bonts'a libaka tsa bokaholimo ba mGluR5 bokong; amygdala, hippocampus, striatum, NA, le cortex ea pele. Li-syndromes tsa kelello li lumellana le libaka tseo. ts'ebetso ea mGluR5, e khothalelitsoeng ho amygdala, e kanna ea ba pakeng tsa maikutlo a mantlha a mofuthu, joalo ka matšoenyeho le khatello ea maikutlo. Re hlalositse kamoo litsela tse peli li ka khonehang; Ts'ebetso ea sechaba, le ho ithuta, li ka hokahanya mekhoa e meng. Kahoo, ts'ebetso ea mGluR5 e bontšitse hore e nka karolo ho ithuteng, 'me ka hona, ka ts'ebetso ho hippocampus, NA, le striatum li ka nka karolo mohopolong le moputsong, taolo ea tlhalohanyo le tšusumetso, joalo ka ha li ameha tšebelisong (Sheba le Setšoantšo. 3). Kamora nako, re hlahisitse hore na mGluR5 e ka amana joang le karabelo ea khatello ea maikutlo sechabeng le khaello ea sechaba, e ka bang e loketseng maemo a mangata a kelello. Tafole 2 e fana ka kakaretso ea tikoloho ea ho senyeha ea RDoC, setšoantšo se amanang le kliniki, le karolo ea mGluR5.
Tšoantšiso 4
Setšoantšo sa 4. Kakaretso ea mekhoa ea mGluR5.
TABLE 2
Tafole 2. RDoC le mGluR5.
Litlhaloso tse qetellang
Tlhahlobo ena e hlalositse ho kenya letsoho ha mGluR5 mathateng a ho feto-fetoha ha maikutlo, OCD le bokhoba, 'me ha bo bapisoa le lipatlisiso tsa batho, haholo-holo lipatlisiso tsa PET. Kahoo re bapisa mekhoa e fapaneng ea mekhoa, joalo ka lipatlisiso tsa liphoofolo, MRS, le lithuto tsa PET. Re fana ka maikutlo a hore phello e matla ea ho tšoenyeha e tobileng e tla ba teng haeba kalafo ea antagonistic ea mGluR5 e qalisoa litekong tsa tleliniki ea motho (RDoC). mGluR5 e boetse e tlalehiloe ho FXS, e bonts'itsoeng ke bofokoli ba bohlokoa sechabeng. Ka lebaka leo, ts'ebetso ea mGluR5 e kanna ea se emise feela ts'ebetso e mpe ea lits'ebetso tse mpe tsa valence le lits'ebetso tse khahlisang, empa hape e kenyelletsa ho senyeha lits'ebetsong tsa lits'ebetso tsa maemo a bophelo (RDoC). Sena ke sa bohlokoa haholo tleleniking hobane ho se sebetse hantle ha setjhaba ke sephetho sa bohlokoa sa maemo a bophelo a kelello a kang OCD, khatello ea maikutlo le bokhoba, bo lebisang ho utloeng bohloko bo boholo le litšenyehelo tsa bohlokoa tse sa tobang sechabeng. Mme qetellong, mGluR5 le eona e bonts'itsoe ho ba le karolo e kholo lithahasellong tsa lithethefatsi, ho khothaletsoang hore e bakoe haholo ke ho eketsa boleng ba moputso oa lithethefatsi. MGluR5 ho kenella ho hanyetsaneng ho ka re thusa haholo bakeng sa kalafo ea ho tšoenyeha ka methapo, le ho ntlafatsa boikhathatso ba khatello ea maikutlo sechabeng le ts'ebetsong ea sechaba.
Tlhōlisano ea Tlhaloso
Ngaka Terbeck, Dr Chesterman, le Dr Akkus ha ba na likhohlano tsa thahasello. Ngaka Hasler o amohetse chelete ea lithuso ho tsoa ho Novartis, e hlahisang le ho leka lithethefatsi tse lebisang mGluR5.
References
Abe, T., Sugihara, H., Nawa, H., Shigemoto, R., Mizuno, N., le Nakanishi, S. (1992). Tšobotsi ea molek'hule ea noab metropotic glutamate receptor mGluR5 e kopantsoeng le phetisetso ea pontso ea inositol phosphate / Ca2. J. Biol. CHEM. 267, 13361-13368.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Agid, Y., Buzsáki, G., litaemane, DM, Frackowiak, R., Giedd, J., Girault, J.-A., et al. (2007). Ho sibolloa ha lithethefatsi bakeng sa mafu a kelello ho ka ntlafatsoa joang? Nat. Motsoako oa litheko tsa lithethefatsi. 6, 189-201. Doi: 10.1038 / nrd2217
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Akkus, F., Ametamey, SM, Treyer, V., Burger, C., Johayem, A., Umbricht, D., et al. (2013). Ts'oaetso e tšoaoang ea lefats'e ea mGluR5 receptor e tlamang batho ba tsubang le ba tsubang nakong e fetileng e boletsoeng ke [11C] ABP688 positron emission tomography. Proc. Natl. Acad. Sci. USA. 110, 737-742. Doi: 10.1073 / pnas.1210984110
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Akkus, F., Terbeck, S., Ametamey, SM, Rufer, MD, Treyer, V., Burger, C., et al. (2014). Metabotropic glutamate receptor 5 e tlamang ho bakuli ba nang le bothata bo potelletseng. Int. J. Neuropsychopharmacol. 17, 1915-1922. Doi: 10.1017 / S1461145714000716
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Ametamey, SM, Kessler, LJ, Honer, M., Wyss, MT, Buck, A., Hintermann, S., et al. (2006). Radiosynthesis le tlhahlobo ea preclinical ea11CABP688 joalo ka probe ea ho nahana ka metabotropic glutamate receptor subtype 5. J. Nucl. Moedi. 47, 698-705.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Anderson, JJ, Bradbury, MJ, Giracello, DR, Chapman, DF, Holtz, G., Roppe, J., et al. (2003). Ka vivo receptor ho lula ha bahanyetsi ba mGlu5 ba sebelisang radioligand e ncha [3 H] 3-methoxy-5- (pyridin-2-ylethynyl) pyridine). EUR. J. Pharmacol. 473, 35–40. doi: 10.1016/S0014-2999(03)01935-6
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Ahnaou, A., Raeymaekers, L., Steckler, T., le Drinkenbrug, WHIM (2015). Ho hlahisoa ha metabotropic glutamate receptor (mGluR5) molomong oa potoloho ea boroko ba NREM-REM le homeostasis: bopaki bo tsoang ho litoeba tsa mGluR5 (- / -). Behav. Resin ea Boko. 282, 218-226. Doi: 10.1016 / j.bbr.2015.01.009
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Bear, MF, Huber, KM, le Warren, ST (2004). Khopolo ea mGluR ea ho fokola kelellong ha kelello X. Trends Neurosci. 27, 370-377. Doi: 10.1016 / j.tins.2004.04.009
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Berg, D., Godau, J., Trenkwalder, C., Eggert, K., Csoti, I, Storch, A., et al. (2011). Kalafo ea AFQ056 ea dyskinesias ea levodopa-ikiwa: sephetho sa liteko tsa 2 tse laoloang ka boomo. Tsamaisa. Khahlano. 26, 1243-1250. Doi: 10.1002 / mds.23616
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., et al. (2009). Lebitso la sefofane le bulehileng, teko e le 'ngoe ea fenobam ho batho ba baholo ba nang le lefu la X. J. Med. Liphatsa tsa lefutso. 46, 266-271. Doi: 10.1136 / jmg.2008.063701
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Bisaga, A., Danysz, W., le Foltin, RW (2008). Ho tsofala ha glutamatergic NMDA le li-mGluR5 receptors li fokotsa ts'ebeliso ea lijo ka mofuta oa mofuta oa mofuta oa mofuta oa ho ja ho itlopa. EUR. Neuropsychopharmacol. 18, 794-802. Doi: 10.1016 / j.euroneuro.2008.05.004
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Boer, K., Encha-Razavi, F., Sinico, M., le Aronica, E. (2010). Phapang e fapaneng ea li-receptors tsa sehlopha sa metabotropic glutamate ho nts'etsapele cortex ea motho. Resin ea Boko. 1324, 24-33. Doi: 10.1016 / j.brainres.2010.02.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Brennan, BP, Rauch, SL, Jensen, JE, le Mopapa, HG (2012). Tlhahlobo e nyarosang ea lithuto tsa maqhubu a khanya ea matla a khoheli. Biol. Psychiatry 73, 31-24. doi: 10.1016 / j.biopsych.2012.06.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Burket, JA, Benson, AD, Tang, AH, le Deutsch, SI (2014). Rapamycin e ntlafatsa boiketlo ba batho ho mofuta oa panya ea BTBR ea likotsi tsa Autism. Brain Res. Bull. 100, 70-75. Doi: 10.1016 / j.brainresbull.2013.11.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Chiamulera, C., Epping-Jordan, MP, Zocchi, A., Marcon, C., Cottiny, C., Tacconi, S., et al. (2001). Ho matlafatsa le litlamorao tse matlafatsang tsa koae ha li eo ho litoeba tsa mouta tse ling. Nat. Neurosci. 4, 873-874. Doi: 10.1038 / nn0901-873
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Chung, W., Choi, SY, Lee, E., Park, H., Kang, J., Park, H., et al. (2015). Liphoso tsa sechaba ho IRSp53 litoeba tsa phetoho e ntlafalitsoeng ke khatello ea NMDAR le mGluR5. Nat. Neurosci. 18, 435-442. Doi: 10.1038 / nn.3927
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Cleva, RM, le Olive, MF (2011). Li-modulators tse sebetsang tsa allosteric tsa mofuta oa 5 metabotropic glutamate receptors (mGluR5) le monyetla oa tsona oa kalafo bakeng sa kalafo ea lits'oaetso tsa CNS. Limolek'hule 16, 2097-2106. Doi: 10.3390 / limolek'hule16032097
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Deschwanden, A., Karolewicz, B., Feyissa, AM, Treyer, V., Ametamey, SM, Johayem, A., et al. (2011). Fokotsa metabotropic glutamate receptor 5 density maemong a maholo a sithabetseng a khethiloeng ke [(11) C] ABP688 PET le thuto ea postmortem. Am. J. Psychiatry 168, 727-734. doi: 10.1176 / appi.ajp.2011.09111607
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Erickson, CA, Mullett, JE, le McDougle, CJ (2009). Memeline ea Open-labeline ho ramatiki ea X e fokolang. J. Autism Dev. Khahlano. 39, 1629-1635. doi: 10.1007 / s10803-009-0807-3
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Erickson, CA, Qalong, M., Stigler, KA, Wink, LK, Mullett, JE, le McDougle, CJ (2011). Phuputso e bulehileng ea tlhaho ea sefofane sa acamprosate ho bacha ba nang le lefu la autistic. J. Ngoana Adolesc. Psychopharmacol. 21, 565-569. Doi: 10.1089 / cap.2011.0034
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pele, MB, le Gibbon, M. (1997). Tataiso ea mosebelisi bakeng sa Puisano e hlophisitsoeng ea Kliniki bakeng sa DSM-IV Axis I Disorders SCID-I: Clinician Version. New York, NY: American Psychiatric Pub.
Feyissa, AM, Chandran, A., Stockmeier, CA, le Karolewicz, B. (2009). Maemo a fokotsehileng a NR2A le NR2B subunits ea NMDA receptor le PSD-95 ka pele ho cortex ea khatello ea maikutlo. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 70-75. Doi: 10.1016 / j.pnpbp.2008.10.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Garber, KB, Visootsak, J., le Warren, ST (2008). Fragile X syndrome. EUR. J. Hum. Liphatsa tsa lefutso. 16, 666-672. Doi: 10.1038 / ejhg.2008.61
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Gass, JT, Osborne, MP, Watson, NL, Brown, JL, le Olive, MF (2009). antGonR5 antagonism e bonts'a methapo ea methamphetamine mme e thibela ho khutlisetsoa ha boitšoaro bo batlang methamphetamine litšoantšong. Neuropsychopharmacology. 34, 820-833. Doi: 10.1038 / npp.2008.140
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Harvey, BH, le Shahid, M. (2012). Metabotropic le ionotropic glutamate receptors joalo ka liphofu tsa neurobiological ho matšoenyeho le mathata a amanang le khatello ea maikutlo: tsepamisa maikutlo ho pharmacology le mehlaleng ea pele ea phetolelo. Pharmacol. Likokoana-hloko. Behav. 100, 775-800. Doi: 10.1016 / j.pbb.2011.06.014
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., LaSalle-Ricci, VH, Ronquillo, JG, Crawley, SA, Cochran, LW, Kazuba, D., et al. (2005). Mats'oao a bonts'ang a ho qobella-ho qobella matšoao a bonts'a likamano tse ikhethileng ho comorbidity ea kelello. Resp Psychiatry. 135, 121-132. Doi: 10.1016 / j.psychres.2005.03.003
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., van der Veen, JW, Tumonis, T., Meyers, N., Shen, J., le Drevets, WC (2007). Fokotsa li-glutamate / glutamine le maemo a γ-aminobutyric acid maemong a sithabetsang a nang le khatello e kholo ea maikutlo a sebelisang proton magnetic resonance spectroscopy. Khoto. Gen. Psychiatry 64, 193-200. doi: 10.1001 / archpsyc.64.2.193
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., van der Veen, JW, Geraci, M., Shen, J., Pine, D., le Drevets, WC (2009). Litekanyetso tsa pele tsa cortical gamma-aminobutyric acid pele ho tšenyo ea tšabo e khethiloeng ke proton magnetic resonance spectroscopy. Biol. Psychiatry 65, 273-275. doi: 10.1016 / j.biopsych.2008.06.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hefti, K., Holst, SC, Sovago, J., Bachmann, V., Buck, A., Ametamey, SM, et al. (2013). Ho eketseha ha metabotropic glutamate receptor subtype 5 bokong ba motho kamora bosiu bo le bong ntle le boroko. Biol. Psychiatry 73, 161-168. doi: 10.1016 / j.biopsych.2012.07.030
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hyman, SE (2005). Tlatsetso: bokuli ba ho ithuta le ho hopola. Am. J. Psychiatry 162, 1414-1422. doi: 10.1176 / appi.ajp.162.8.1414
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hoffpauir, BK, le Gleason, EL (2002). Ho kenya ts'ebetso ea li-modGates tsa mGluR5 moduli tsa GABAA receptor liseleng tse khutlang. J. Neurophysiol. 88, 1766-1776.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Hulka, LM, Treyer, V., Scheidegger, M., Preller, KH, Vonmoos, M., Baumgartner, MR, et al. (2014). Ho tsuba empa ho se ts'ebeliso ea koae ho kopantsoe le "cervine" ea methapo e nyane ea calcam e fumanehang bathong. Mol. Psychiatry 19, 625-632. Doi: 10.1038 / mp.2013.51
Text e feletseng ea CrossRef | Google Setsebi
Kalivas, PW, le Volkow, ND (2005). Motheo oa bokhoba ba ho lemalla: mokhoa oa tšusumetso le khetho. Am. J. Psychiatry 162, 1403-1413. doi: 10.1176 / appi.ajp.162.8.1403
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Kalivas, PW (2009). The glutamate homeostasis hypothesis ea ho lemalla. Nat. Rev. Neurosci. 10, 561-572. Doi: 10.1038 / nrn2515
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Krystal, JH, Mathew, SJ, D'Souza, DC, Garakani, A., Gunduz-Bruce, H., le Charney, DS (2010). Likopo tse ka bang teng tsa mafu a kelello tsa li-agonists tsa metabotropic glutamate receptor le bahanyetsi. Lithethefatsi tsa CNS 24, 669–693. doi: 10.2165/11533230-000000000-00000
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Kupila, J., Kärkkäinen, O., Laukkanen, V., Tupala, E., Tiihonen, J., le Storvik, M. (2012). mGluR1 / 5 li-receptor densities tse bokong ba litaba tsa joala: Phuputso e entsoeng ka likarolo tsohle tsa hemisphere. Resp Psychiatry. 12, 149-155. Doi: 10.1016 / j.pscychresns.2012.04.003
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Koros, E., Rosenbrock, H., Birk, G., Weiss, C., le Sams-Dodd, F. (2007). MGlu5 mokhethi receptor antagonist MTEP, e ts'oanang le bahanyetsi ba li-receptor ba NMDA, e etsa hore ho be le nako ea ho itšehla thajana ka likhoto. Neuropsychopharmacology 32, 562-576. doi: 10.1038 / sj.npp.1301133
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Lea, PM, le Faden, AI (2006). Metabotropic glutamate receptor subtype 5 antagonists MPEP le MTEP. Rev Rev Drug Rev. 12, 149-166. Doi: 10.1111 / j.1527-3458.2006.00149.x
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Legutko, B., Szewczyk, B., Pomierny-Chamioło, L., Nowak, G., le Pilc, A. (2006). Phello ea kalafo ea MPEP ho polelo ea tlhaho ea neurotrophic factor gene. Pharmacol. Rep. 58, 427-430.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Luykx, JJ, Laban, KG, van den Heuvel, MP, Boks, MPM, Mandl, RCW, Kahn, RS, et al. (2012). Karolo ea tikoloho le boemo bo ikhethileng ba glutamate bothateng bo boholo ba khatello ea maikutlo: tlhahlobo ea meta-ea (1) liphumano tsa H-MRS. Neurosci. Biobehav. Tšen. 36, 198-205. Doi: 10.1016 / j.neubiorev.2011.05.014
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Meldrum, BS (2000). Glutamate e le neurotransmitter bokong: tlhahlobo ea physiology le pathology. J. Nutr. 130, 1007.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Morris, SE, le Cuthbert, BN (2012). Tlhahlobo ea Domain ea Patlisiso: Lits'ebetso tsa kelello, li-circuits tsa neural, le boholo ba boitšoaro. Clin ea Dialogues. Neurosci. 14, 29-37.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Olive, MF (2005). Li-receptors tsa mGlu5: neuroanatomy, pharmacology, le karolo ho tlatseng lithethefatsi. Borr. Rev Psychchi Rev. 1, 197-214. Doi: 10.2174 / 1573400054065578
Text e feletseng ea CrossRef | Google Setsebi
Phan, KL, Fitzgerald, DA, Cortese, BM, Seraji-Bozorgzad, N., Tancer, ME, le Moore, GJ (2005). Anterior cingrate neurochemistry ho mathata a ho tšoenyeha ka sechaba: 1H-MRS ho 4 Tesla. Neuroreport 16, 183–186. doi: 10.1097/00001756-200502080-00024
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pittenger, C., Krystal, JH, le Coric, V. (2006). Lithethefatsi tse fanang ka maikutlo a glutamate e le mahlahana a li-pharmacotherapeutic kalafong ea ts'oaetso ea khatello e matla. NeuroRx 3, 69-81. Doi: 10.1016 / j.nurx.2005.12.006
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pollack, MH, Jensen, JE, Simon, NM, Kaufmann, RE, le Renshaw, PF (2008). Boithuto bo phahameng ba MRS ba GABA, glutamate le glutamine bothateng ba matšoenyeho a sechaba ?: karabelo kalafong e nang levetiracetam. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 739-743. Doi: 10.1016 / j.pnpbp.2007.11.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Riaza Bermudo-Soriano, C., Perez-Rodriguez, MM, Vaquero-Lorenzo, C., le Baca-Garcia, E. (2012). Mehopolo e ncha ho glutamate le matšoenyeho. Pharmacol. Likokoana-hloko. Behav. 100, 752-774. Doi: 10.1016 / j.pbb.2011.04.010
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Riedel, G., Casabona, G., Platt, B., Macphail, EM, le Nicoletti, F. (2000). Tšabo e nang le tšabo ea nako le tlhoko-tlatsetso e ikhethang ea polelo ea mGlu5 ea protein receptor ho rat hippocampus. Neuropharmacology 39, 1943–1951. doi: 10.1016/S0028-3908(00)00037-X
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Rutten, K., De Vry, J., Bruckmann, W., le Tzschentke, TM (2011). Pharmacological blockade kapa "genetic knockout" ea NOP receptor e hlahisa litholoana tse matlafatsang tsa morphine ho likhoto. Lithethefatsi. 114, 253-256. Doi: 10.1016 / j.drugalcdep.2010.10.004
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Romano, C., van den Pol, AN, le O'Malley, KL (1996). Pontšo e ntlafalitsoeng ea nts'etsopele ea metabotropic glutamate receptor mGluR5 bokong ba rat: protheine, mRNA splice variets, le kabo ea libaka. J. Bapisa. Neurol. 367, 403-412.
Rosenberg, DR, le Keshavan, MS (1998). Ho mofuta oa neurodevelopmental oa lefu le lemalloang. Biol. Psychiatry 43, 623–640. doi: 10.1016/S0006-3223(97)00443-5
Text e feletseng ea CrossRef | Google Setsebi
Sanacora, G., Zarate, CA, Krystal, JH, le Manji, HK (2008). Ho shebella tsamaiso ea glutamatergic ho nts'etsopele rialo, kalafo e ntlafalitsoeng bakeng sa mathata a maikutlo. Nat. Motsoako oa litheko tsa lithethefatsi. 7, 426-437. Doi: 10.1038 / nrd2462
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Schoepp, DD (2001). Ho senola mesebetsi ea li-receptors tsa presynaptic metabotropic glutamate tsamaisong ea methapo e bohareng. J. Pharmacol. Hlakola Ther. 299, 12-20.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Segrin, C. (2000). Khaello ea litsebo tsa kahisano e amanang le khatello ea maikutlo. Clin. Psychol. Tšen. 20, 379–403. doi: 10.1016/S0272-7358(98)00104-4
Text e feletseng ea CrossRef | Google Setsebi
Simonyi, A., Schachtman, TR, le Christoffersen, GR (2010). Metabotropic glutamate receptor subtype 5 antagonism ho ithuta le ho hopola. EUR. J. Pharmacol. 639, 17-25. Doi: 10.1016 / j.ejphar.2009.12.039
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Soares, DP, le Molao, M. (2009). Magnetic resonance visroscopy ea boko: tlhahlobo ea metabolites le ts'ebeliso ea bongaka. Clin. Radiol. 64, 12-21. Doi: 10.1016 / j.crad.2008.07.002
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Swanson, CJ, Bures, M., Johnson, MP, Linden, A-M., Monn, JA, le Schoepp, DD (2005). Metabotropic glutamate receptors joalo ka liphofu tse ncha tsa lipelaelo le khatello ea maikutlo. Nat. Motsoako oa litheko tsa lithethefatsi. 4, 131-144. Doi: 10.1038 / nrd1630
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Szeszko, PR, Christian, C., Macmaster, F., Lencz, T., Mirza, Y., Taormina, SP, et al. (2008). Litaba tse fetohileng tsa sebopeho litabeng tsa psychotropic tse nang le khatello ea kelello ea bohlasoa ba bana: thuto e ntlafalitsoeng ea voxel-based morphometry. Am. J. Psychiatry 165, 1299-1307. doi: 10.1176 / appi.ajp.2008.08010033
Text e feletseng ea CrossRef | Google Setsebi
Tatarczyńska, E., Klodzińska, A., Chojnacka-Wójcik, E., Palucha, A., Gasparini, F., Kuhn, R., et al. (2001). Lisosa tse ka 'nang tsa bakoa ke ho tšoenyeha ka maikutlo le litla-morao-morao tsa MPEP, mohanyetsi ea matla le ea sebetsang oa mGlu5 receptor. Br. J. Pharmacol. 132, 1423-1430. Doi: 10.1038 / sj.bjp.0703923
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Tronci, V., Vronskaya, S., Montgomery, N., Mura, D., le Balfour, DJK (2010). Litlamorao tsa mGluR5 receptor antagonist 6-methyl-2- (phenylethynyl) -pyridine (MPEP) mabapi le likarabo tsa boitšoaro ho nicotine. Psychopharmacology 211, 33–42. doi: 10.1007/s00213-010-1868-x
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Van den Heuvel, OA, Remijnse, PL, Mataix-Cols, D., Vrenken, H., Groenewegen, HJ, Uylings, HBM, et al. (2009). Matšoao a ka sehloohong a pherekano e sa bonahaleng e khothalletsoang ke tsamaiso ea methapo e ikhethileng. boko 132, 853-868. Doi: 10.1093 / boko / awn267
Text e feletseng ea CrossRef | Google Setsebi
Wagner, KV, Hartmann, J., Labermaier, C., Häusl, AS, Zhao, G., Harbich, D., et al. (ka khatiso). Mesebetsi ea Homer1 / mGluR5 e kotsing ea ho ba le khatello ea maikutlo ea maemo a bophelo sechabeng. Neuropsychopharmacology. Doi: 10.1038 / npp.2014.308
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Yüksel, C., le Öngür, D. (2010). Magnetic resonance visroscopy lithuto tsa tlhekefetso tse amanang le glutamate mathateng a maikutlo. Biol. Psychiatry 68, 785-794. doi: 10.1016 / j.biopsych.2010.06.016
Text e feletseng ea CrossRef | Google Setsebi
Zarei, M., Mataix-Cols, D., Heyman, mimi, Hough, M., Doherty, J., Burge, L., et al. (2011). Liphetoho tsa bophahamo ba taba ea bohlooho le bosoasoi bo bosoeu ho bacha ba nang le bothata ba ho bona lintho li ba tsamaela hantle. Biol. Psychiatry 70, 1083-1090. doi: 10.1016 / j.biopsych.2011.06.032
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Mantsoe a bohlokoa: mGluR5, PET, mathata a maikutlo, ho lemalla, ho tšoenyeha
Caring: Terbeck S, Akkus F, Chesterman LP le Hasler G (2015) Karolo ea metabotropic glutamate receptor 5 ho pathogeneis ea mathata a maikutlo le ho lemalla: ho kopanya bopaki ba preclinical le lithuto tsa motho tsa Positron Emission Tomography (PET). Ka pele. Neurosci. 9: 86. Doi: 10.3389 / fnins.2015.00086
E amohetsoe: 07 Januari 2015; E amohetsoe: 27 February 2015;
E hatisitsoe: 18 March 2015.
E hlophisitsoeng ke:
Ashok Kumar, Univesithi ea Florida, USA
Hlahloba by:
Karthik Bodhinathan, Setsi sa Patlisiso ea Bongaka Sanford Burnham, USA
Amber M. Muehlmann, Univesithi ea Florida, USA
Copyright © 2015 Terbeck, Akkus, Chesterman le Hasler. Ena ke sengoloa se bulehileng se fihletsoeng ka tlase ho License ea Boikarabelo ba Creative Commons (CC BY). Ho sebelisoa, ho abeloa kapa ho hlahisa liforomo tse ling ho lumelloa, hafeela bangoli ba pele kapa ba le lengolo la tumello ba tlotlisoa le hore sengoliloeng sa pele sa makasine ena se boleloa, ho latela mokhoa o amohelehang oa thuto. Ha ho sebelisoe, ho abeloa kapa ho hlahisa ho lumelloa ho sa lumellaneng le melao ena.
* Litaba: Sylvia Terbeck, Sekolo sa Psychology, Setsi sa Bophelo le Saense ea Batho, Univesithi ea Plymouth, PL4 8AA, Plymouth, UK [imeile e sirelelitsoe]
Bofokoli ba kelello le tlholeho e ipapisitseng le batho ba bang
Mathata a kelello a mangata haholo 'me' mele o lula o kopane 'meleng. Leha ho le joalo, liphekolo tse tloaelehileng tsa kalafo ea meriana ea mafu a kelello li thehiloe ho mekhoa e fokolang ea pathophysiological, ka mohlala, ho eketsa ho fumaneha ha monoamine ka matšoenyeho le khatello ea maikutlo. Kahoo, ho na le tlhoko e potlakileng ea ho ntlafatsa le ho ntšetsa pele liphekolo tsa mafu a kelello, mme ho kenella hoa meriana litabeng tsa metabotropic ke tsoelo-pele e tšepisang ntlheng ena (Agid et al., 2007).
Liteko tse ngata tsa batho li entsoe linyeoeng tsa Fragile X Syndrome (FXS). Khopolo ea mGluR5 ea FXS e tiisa hore ho haella ha protheine ea kelello ea kelello ea reteleha X (FMRP) ho fella ka ho hlahisa signutamatergic ho feteletseng ka mGluR5 (Bear et al., 2004). Sena se lebisa ho phetolelo ea lehae ea mRNA sebakeng sa synapse hobane FMRP ha e teng ho laola ts'ebetso. Qetellong, sena se fokolisa ho nyefola le ho baka palo e eketsehang ea methapo ea methapo e sa sebetseng, e ka hlalosang ho holofala ha mahlale a fumanoang ho bakuli ba FXS. Bokowa bona bo amahanngwa le matshwao a ho feto-fetoha ha maikutlo le ho tšoenyeha 'me hangata bo ba teng ka lintho tse atileng bothateng ba Autism spectrum disorder, ho kenyelletsa ho lieha ho ntlafatso ea puo le puo, maikutlo a senyehileng a kelello, le ts'ebetso e mpe ea maemo a bophelo le maikutlo, hammoho le boits'oaro bo pheta-phetoang (Garber et al., 2008). Bopaki ba pele le bo sa tobang ba hore mGluR5 antagonist e ka ntlafatsa botsoalle ho FXS (Burket et al., 2014) e phahamisa ts'epo ea hore lithethefatsi tse lebisang mGluR5 e kanna ea ba tsa ts'ebeliso ea bongaka maemong a atileng a kelello a amanang le litsamaiso tse sitisang lits'ebetso tsa maemo a bophelo tse kang autism, schizophrenia, le khatello ea maikutlo. Ntle le moo, mokhoa o shebahalang oa ho pheta-pheta o ka bonoang ho FXS o ka fana ka tlhahiso ea hore ho na le karohano e arolelanoang ea mafu a kelello har'a mafu a mang a mafu a kelello joalo ka ho senyeha ha kelello (OCD) le ho lemalla.
Leha ho bile le keketseho tsebong ea mahlale le lipatlisiso ka mGluR5, boiteko ba nts'etsopele ea lithethefatsi ha bo atlehe (Agid et al., 2007). Lithethefatsi tse lebisang li-receptor tsa ionotropic hangata li hlahisa litlamorao tse ngata mme maano a hona joale a nts'etsopele ea lithethefatsi ha a so hlahise litheko tse khethiloeng bakeng sa li-receptor tsa ionotropic tse ka fokotsang litlamorao tse mpe. Mohlala, bahanyetsi ba ionotropic receptor ba hlahisa litla-morao ho batho tse kenyeletsang ho senyeha hoa memori, liketsahalo tsa kelello le lichapo (Swanson et al., 2005). Litlamorao tse mpe li ka hlaha hobane li-receptor tsa ionotropic glutamate li na le phetisetso e ntle, athe li-receptor tsa metabotropic li sa lekane ebile li ajoa ka mokhoa o khethang (Krystal et al., 2010). Ka lebaka leo, nts'etsopele ea morao-rao ea lithethefatsi e shebile haholo ho likhomphutha tse lebisang li-metabotropic receptors ho nka hore lithethefatsi tse joalo li tla amahanngoa le litlamorao tse fokolang ho feta tse tlamahanang le li-receptor tse sebetsang ka potlako tsa ionotropic.
Likarolong tse latelang, re tla hlahloba bopaki bo tsoang ho lithuto tsa PET tsa batho mabapi le ho nka karolo ha mGluR5 mathateng a maikutlo le ho lemalla le ho bapisa seo ba se fumaneng le lithuto tsa liphoofolo. Ho feta moo, re tla hlalosa libaka tse ling tsa boko bakeng sa ts'ebetso ea mGluR5 ho batho mme qetellong re fane ka tlhahiso ea hore na ts'ebetso ea mGluR5 e tobileng le e sa tobang e ka kenya letsoho joang litabeng tsa kelello tsa batho.
mGluR5, Matšoenyeho a Pathological, le Mathata a Mood
Matšoenyeho a Kelello
Matšoenyeho a lefu la kelello a hlaha mathateng a ho tšoenyeha, ho kenyelletsa ho tšoenyeha ka kakaretso, ho tšoha ka letsoalo (maemo a kelello a atileng haholo lefats'eng ka bophara, Pele le Gibbon, 1997), empa hape le maemong a mang a atileng a kelello a kang ho tepella maikutlo le khatello ea kelello e hlokisang botsitso (OCD). Maemo ana a kelello a baka ho senyeha ho hoholo mosebetsing le mesebetsing, ho lebisang meroalo ea litšenyehelo tsa bophelo bo botle le mahlomola a mokuli (Pele le Gibbon, 1997). Ka kakaretso, matšoenyeho a ka 'na a amahanngoa le thabo e fetisisang ea boko (Harvey le Shahid, 2012).
Patlisiso ea Previrinical Neurobiological
Liphumano tse tsoang lipalo tse ngata tsa liteko tsa liphoofolo tse khethiloeng esale pele li bonts'a phello ea kalafo ea merafo ea mGluR5 ka matšoenyeho. Swanson et al. (2005) e lekola lithuto tsa liphoofolo ka lithethefatsi tse lebisang mGluR5 ho boits'oaro bo joalo ba ho tšoenyeha. Ba ile ba fihlela qeto ea hore kalafo ea ho hanyetsa ka mokhoa oa mGluR5 hangata e lebisa ho likarabo tse tšoenyang ho liphoofolo tse lekang. Haholo-holo, litlamorao tse kang ho fokotseha hoa maemo a ho bata, ho ts'oaroa le ho amoheloa ha kotlo, le ts'ebelisano e kholo li ile tsa bonoa. Mohlala, tekanyetso e le 'ngoe ea 2-methyl-6- (phenylethynyl) pyridine (MPEP) e ekelitse nako ea likhoto tse sebelisitsoeng letsohong le bulehileng la ts'ebetso ea liteko, ntle le ho ama ho hlophisa kapa boits'oaro ba motor (Tatarczyńska et al., 2001). Krystal et al. (2010) e hlahlobe lithuto tsa preclinical tsa liphoofolo tse ileng tsa hlahloba bahanyetsi ba mGluR5 (MTEP, MPEP, fenobam) mefuteng ea mouse ea matšoenyeho. Lithuto tsena li sebelisitse mehato e fapaneng ea sephetho, joalo ka ho felisoa ha boemo ba tšabo le likarabo mohloling o mong o phahameng, ho lekola katleho ea kalafo ea lithethefatsi. Ho lithuto tse hlahlojoang, 88.45% e tlalehile phello ea ho tšoenyeha le bahanyetsi ba mGluR5 (Krystal et al., 2010). Haufinyane tjena, tekolo e 'ngoe mabapi le lipatlisiso tsa matšoenyeho mefuteng ea liphoofolo e ileng ea lekola phello ea ho kenella ha ionotropic le metabotropic glutamate receptor antagonist e phatlalalitsoe (Riaza Bermudo-Soriano et al., 2012). Mabapi le mGluR5, bangoli ba thathamisitse lithuto tsa liphoofolo tsa 43 tsa matšoenyeho, 'me kaofela ntle le tse peli li bontšitse litlamorao tse tšoenyang.
Lithuto tsa Batho
Bopaki ba pele ba khopolo ea hore ts'ebetso ea glutamate ha e sebetse mathateng a ho tšoenyeha e tsoa lipatlisisong tsa MRS. Mohlala, ba sebelisa sebopeho sa maqhubu a maqhubu a 1H se nang le voxel e phahameng, bafuputsi ba fumane hore ha ho bapisoa le taolo e phetseng hantle, bakuli ba nang le bothata ba ho tšoenyeha ka maemo a sechaba ba bontšitse maemo a phahameng haholo a "cortex cortex" ea Aterior.Phan et al., 2005). Ho feta moo, lipatlisiso li fumane ho eketseha ha khatello ea glutamate ea lefatše ho bakuli ba 10 ba nang le phobia ea sechaba (Pollack et al., 2008). Joalokaha ho boletsoe pejana, lithuto tsena, leha ho le joalo, li ne li sa khone ho fumana hore na li-receptors tsa glutamate li amanang le ts'ebetso e feteletseng ea glutamate e ne e le eng.
Re sebelisa mokhoa oa ho etsa lipatlisiso oa PET, haufinyane re bile ba pele ba ho bonts'a likamano lipakeng tsa mGluR5 le matšoenyeho, ho Major Depression Disorder (MDD), le OCD. Phuputsong e le 'ngoe, re entse lipatlisiso tsa mGluR5 Distribution Volume Ratio (DVR) ho bakuli ba 10 ba nang le OCD le 10 taolo e phetseng hantle ba sebelisa [11C] ABP688 PET (Akkus et al., 2014). Re sebelisitse Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) e le tekanyo ea bongaka ea matšoao a OCD. Re hlokometse khokahano ea bohlokoa lipakeng tsa marang-rang a Y-BOCS a ho itlhahisa ka bongata le mGluR5 DVR libakeng tsa amygdala, ACC, le medial orbitofrontal cortex (Akkus et al., 2014). Libaka tsena tsa boko li kile tsa ba le tšusumetso ho OCD pathophysiology. Haele hantle, tlhekefetso ea popelo bokong ho amygdala, ACC le orbitofrontal cortex ka mokhoa o ts'oanang li amahantsoe le OCD (Rosenberg le Keshavan, 1998; Szeszko et al., 2008; Van den Heuvel et al., 2009). Ha ho fanoa ka hore lithuto tsa sebopeho sa monahano li fane ka bopaki ba khokahano e ntle pakeng tsa ho teba ha OCD le bophahamo ba litaba tsa bohlooho (Zarei et al., 2011), ho eketseha ha mGluR5 ho OCD ho ka bontša letsoalo le eketsehang la li-neuron. Leha ho DSM-5 OCD ha e sa nkoa e le bothata ba ho tšoenyeha, bakuli ba OCD ba bangata ba na le matšoao a ho tšoenyeha. Mohlaleng o moholo oa tleliniki, re kile ra supa hore bakuli ba OCD ba nang le ts'oaetso ba na le ts'oaetso e phahameng haholo ea matšoao a ho tšoenyeha le mathata (Hasler et al., 2005). Pampiring ena, re khothalelitse hore maikutlo a kenyelletsang khatello ea maikutlo, matšoenyeho, kapa likhohlano a ka amahanngoa le ho eketseha ha glutamatergic neurotransmission ho amygdala, ACC, le orbitofrontal cortex.
Ha ho kopanngoa hammoho, liphumano tse tsoang lipatlisisong tsa morao-rao tse sebelisang mekhoa e fapaneng ea ho etsa lipatlisiso li ts'ehetsa maikutlo a hore ts'ebetso ea glutamate ha e tloaelehe libakeng tsa bohlokoa tsa tsamaiso ea maoto le methapo ea maikutlo e amanang le ho tšoenyeha. Ts'ebetso e sa tloaelehang e ka boela ea amana le receptor ea mGluR5. Kaha, pele ho tleliniki, le lipatlisiso tsa PET li bonts'itse mokhoa o lumellanang oa sephetho, re fana ka maikutlo a hore kalafo ea mGluR5 e ts'oarehang e ka hlahisa litlamorao tse kholo tsa bakuli ba nang le matšoenyeho a pathological.
Mathata a maholo a khatello ea maikutlo (MDD)
Patlisiso ea Previrinical Neurobiological
Thutong ea bona, Krystal et al. (2010) o hlalositse sephetho sa lithuto tse robeli tse batlisisang mGluR5 antagonists MTEP le MPEP mefuteng ea liphoofolo ea khatello ea maikutlo. Ha ho bapisoa le litekanyetso tsa katleho ea kalafo bakeng sa mathata a ho tšoenyeha, bangoli ba tlaleha hore ke 62.5-75% feela e fumaneng phello e hlakileng ea antidepressant, leha kalafo e sebelisitsoe le ionotropic NMDA ketagonist ketamine e bontšitsoe ho lebisa litlamorao tse potlakileng tsa kalafo, esita le ho bakuli ba hanyetsang kalafo.Pittenger et al., 2006).
Lithuto tsa Batho
Tlhahlobo ea morao-rao e hlahlobe lithuto tsa 13 MRS tsa mathata a maikutlo. Bangoli ba tlaleha hore lithuto tsena li lula li fumana bopaki ba hore glutamate e fokotsehile ho MDD (Hasler et al., 2007; Yüksel le Öngür, 2010). Haholo-holo, litekanyetso tse fokotsang tsa glutamate ho ACC, li-cortex tsa dorsolateral pele pele, corsex ea dorsomedial pre mapemaal, cortex ea ventromedial prewardal precyal, amygdala, le hippocampus. Tlhahlobo ea morao-rao mabapi le lithuto tse sebelisang MRS ho hlahloba glutamate ho MDD e tiisitse hore khatello ea glutamate ho ACC e fokotsehile kamehla (Luykx et al., 2012). Ka occipital cortex, glutamate e eketsehileng e fumanoe ke bafuputsi ba bang, ba neng ba le kaholimo ho sehlopha sa bakuli ba MDD (se phahameng ka ho fetisisa sa melancholic).Sanacora et al., 2008).
Phuputsong e fetileng, re fumane litšoantšo tsa PET tsa mGluR5 receptor e tlamang lithutong tse sa ngolisoang tsa 11 tse nang le li -DD le li-11 li-control tsa bophelo bo botle (Deschwanden et al., 2011). Re fumane ho fokotseha ha tikoloho ea mGluR5 e tlamang ka cortex ea pele, cingrate cortex, insula, thalamus, le hippocampus ea bakuli ba nang le khatello ea maikutlo. Ntle le moo, botebo ba khatello ea maikutlo bo amanang le mGluR5 e tlamang hippocampus. Re khothalelitse hore liphumano tsena li bonts'e li-neurotransication tse fokotsehileng tsa mGluR5 ho tepelletseng maikutlong, mohlomong ka lebaka la liphetoho tsa basal kapa tse tlatselletsang ts'ebetsong ea tsamaiso ea glutamate. Ntle le moo, re ile ra hlahloba palo ea polelo ea mGluR5 ho li-sampuli tsa boko ba post-mortem tsa lithuto tse sithabetseng tsa 15 le li-taolo tse tšoanang tsa 15 (Deschwanden et al., 2011). Re bone ho fokotseha ha polelo ea mGluR5 ho preortal ea cortex ho mehlala e fumanoeng ho batho ba tepelletseng maikutlo. Polelo ea receptor e fokotsitsoeng ea NMDA bokong ba kamora lefu-lefu la bakuli ba tepelletseng le eona e tlalehiloe (Feyissa et al., 2009). Kannete, ho kile ha etsoa tlhahiso ea hore litheko tsa antidepressant tsa mGluR5 antagonists li ka kenyelletsa ho thibeloa ha li-receptor tsa NMDA. Sena se ka 'na sa sebetsa pakeng tsa methapo ea kutlo le / kapa ho kenyelletsa polelo ea tlhaho ea neurotropic factor ka hippocampus (Legutko et al., 2006). Ho feta moo, phuputso ea morao-rao e bontšitse hore ho hloka boroko ho eketsa ho fumaneha ha mGluR5 ho batho ba phetseng hantle (Hefti et al., 2013). K'homphieutheng ea anterior cingulate cortex, insula, medial tempobe lobe, parahippocampal gyrus, striatum le amygdala, keketseho ena e hokahane haholo le katleho ea boroko ba boroko joalo ka ha e bontšoa ke boroko bo eketsehileng bo ikhethileng. Phuputso ena e fana ka maikutlo a hore keketseho ea mGluR5 e kanna ea ba sesebelisoa sa methapo ea kutlo se hlalosang ts'ebeliso e ntle ea khatello ea boroko. Liphuputso tse entsoeng esale pele li tiisa kamano ea rona e ikemiselitseng lipakeng tsa mGluR5, boroko le khatello ea maikutlo. Haholo-holo, phuputso e entsoeng ho litoeba tsa mGluR5 e fana ka bopaki ba bohlokoa ba hore mGluR5 e kentse letsoho ho theheng botsitso ba maemo a boroko a NREM a ho robala-REM, ts'ebetso ea NREM butle-butle le karabelo ea homeostatic ho lahleheloeng ke boroko (Ahnaou et al., 2015).
Ho akaretsa, ho na le bopaki bo fetohang bo tsoang liphuputsong tsa liphoofolo, postmortem, MRS, le PET tsa hore sisteme ea "glutamate" e bohlokoa e kentse letsoho ho pathophysiology ea MDD. Leha ho le joalo, bopaki bo fana ka maikutlo a hore ho qhekella ha mGluR5 ho ka 'na ha se ke ha thusa ka ho toba bakuli ba nang le MDD. Sena se tsamaisana le ho fumana ha rona polelo e fokotsitsoeng ea mGluR5 ho bakuli ba MDD. Ho ka nahanoa hore lithethefatsi tse shebileng sisteme ea mGluR5 li ka ba molemo haholo ho bakuli ba sithabetseng ba nang le matšoenyeho a comorbid, mathata a ho lemalla le / kapa lithothokiso tse potileng tsa circadian. Ho feta moo, mathata a teng litsing tsa lits'ebetso tsa maemo a bophelo a tloaelane le MDD. Tsebo e fokolang ea sechaba e bonahala e le karolo ea bohlokoa ea kotsi ea khatello ea maikutlo (Segrin, 2000). Liphoso tse joalo li kenyeletsa boits'oaro ba puo le lipuo, le litšitiso ponahalong ea sefahleho, mahlo, boemo le boitšisinyo, tse ka bapisoang le tse bonoang ho FXS le autism spectrum disorder. Ntle le moo, malebana le litsebo tsa maemo a bophelo, liteko tsa litoeba tse pepesitsoeng khatello ea maikutlo ea sechaba li bonts'itse hore Homer1 / mGluR5 coupling e sitisitsoe, ho fana ka maikutlo a hore bosiu ba mGluR5 bo leka ka matla ho hlaseloa habonolo ha khatello ea maikutlo sechabeng (Wagner et al., Ka khatiso). Ntle le moo, mehlaleng ea litoeba tsa bofokoli ba sechaba, khatello ea mGluR5 e lebisitse ho tloaelano ea litšebelisano tsa sechaba (Chung et al., 2015). Ka bobeli, lithuto tsena li fana ka bopaki ba pele ba hore mGluR5 e bapala likarolo tsa bohlokoa lisosa tsa bophelo ba khatello ea maikutlo le bofokoli ba sechaba bo atisang ho hlokomeloa hangata ho bakuli ba tepelletseng maikutlo. Ka lebaka leo, lithethefatsi tse lebisang mGluR5 li ka bapala karolo ea bohlokoa ho thibela nts'etsopele ea khatello ea maikutlo ho bacha ba nang le bofokoli ba sechaba mme e ka thusa ho phekola bofokoli ba sechaba le ts'ebetso e tlase ea kelello ho bakuli ba MDD.
mGluR5 le Tlatsetso
Ho lemalla ho bonahatsa tšebeliso ea lithethefatsi tse tsoelang pele le ha ho bile le litlamorao tse mpe, liteko tse sa atleheng khafetsa tsa ho emisa kapa ho fokotsa tšebeliso ea lithethefatsi, le matšoao a ho mamella le ho tlohela. Le ha tsamaiso ea dopamine e bapala karolo ea bohlokoa ts'ebetsong ea moputso o matla (Kalivas le Volkow, 2005), ho na le bopaki bo ntseng bo eketseha bo tlatselletsang glutamatergic neurotransication tlatsong (Krystal et al., 2010).
Patlisiso ea Previrinical Neurobiological
Ho 2001, thuto ea seminal ho mGluR5 le papatso li phatlalalitsoe (Chiamulera et al., 2001). Bangoli ba bontšitse hore litoeba tse haelloang ke li-receptor tsa mGluR5 li ile tsa sitoa ho ipata kahare ho sa le ho bonts'a litekanyetso tse eketsehileng tsa extracellular dopamine ka har'a li-nucleus tse latelang kamora ho kenella ka bongata. Liphuputso tse ngata tsa ho latela liphoofolo li bontšitse hore mGluR5 receptor antagonists MPEP le MTEP li fokotsa ho itaola ha lithethefatsi tse lemalloang tse kang cocaine le nikotine (Kalivas, 2009). Olive (2005) e ile ea lekola lithuto tsa liphoofolo tse amanang le tšebeliso ea lithethefatsi 'me ea khothaletsa hore ho na le bopaki ba hore mGluR5 e ka ameha nts'etsopele, ho bona moputso le ho khutlisetsa tšebeliso ea lithethefatsi joalo ka cocaine, morphine, nikotine le ethanol. Bangoli ba hlalositse bopaki bo tsoang liphuputsong tsa liphoofolo hore menahano ea mGluR5 e fokotsa boikemelo ba lithethefatsi, le boitšoaro bo latelang ba ho batla lithethefatsi. Mohlala, haufinyane tjena, ho ile ha fumaneha mofuta oa mofuta oa mofuta oa bothateng ba ho ja lijo tse bobebe hoo MTEP e ileng ea fokotsa tšebeliso ea lipompong ntle le ho fetola boits'oaro ba ho batla lipompong (Bisaga et al., 2008). Patlisiso e khothalelitse hore ho fokotseha ha tšebeliso ea lijo tse amanang le tšebeliso ea litheko tsa mGluR5 receptor ho ka amana le phokotso ea boleng bo putsa ba khothatso e matlafatsang (Bisaga et al., 2008). Ntle le moo, lipatlisiso li tlaleha keketseho e kholo ea maemo a mGluR5 mRNA ho li-bokellane tsa nucleus le dorsolateral striatum kamora ho phetoa khafetsa ha koae ho litoeba tsa liteko (Bisaga et al., 2008).
Lithuto tsa Batho
U sebelisa li-autoradiography ho li-sampole tsa boko tsa post-mortem tse fumanoeng ho bakuli ba nang le mathata a joala le taolo e phetseng hantle, patlisiso e fumane 30-40% e phahameng mGluR1 / 5 e tlamang letsoalo ho hippocampus le striatum ho bakuli ba nang le mathata a joala (Kupila et al., 2012). Seo ba se fumaneng se bonts'itse hore mGluR5 receptor density e kanna ea eketseha libakeng tse ling tsa boko ba bakuli ba lemaletseng joala. Haufinyane tjena re sebelisitse PET ho lekanya li-receptor tsa mGluR5 bokong ba batho ba nang le lithethefatsi tsa nikotine (Akkus et al., 2013). Re fumane phokotseho ea lefats'e ea mGluR5 DVR litabeng ea bohlooho ea batho ba tsubang ba 14 ha ba bapisoa le batho ba sa tsubang (Bona setšoantšo. 2). Phokotso e hlahelletseng e fumanoe ka letsohong le letona le ka ho le letšehali la medial orbitofrontal cortex. Re khothalelitse ho fokotseha hona ha li-receptor tsa mGluR5 e ka ba phetoho ea nako e telele ea ho eketseha ho sa feleng ha glutamate e susumetsoang ke tsamaiso ea nicotine e sa foleng. Tloaelo ena e bonahala e khethehile ts'ebeliso ea nicotine kaha e sa fumanehe ho basebelisi ba koae ba sa tsubeng.Hulka et al., 2014).
Tšoantšiso 2
Setšoantšo sa 2. Setšoantšo se bonts'a bokaholimo bo akaretsang ba mGluR5 DVR ka lihlopha tse tharo tsa tlhahlobo. Ho bokelloa ha kelello ho bonahala ho fokotsehile ka lihlopha tsa batho ba tsubang le ba tsubang. Litšoantšo li baloa ke mofuta oa software ea PMOD 3 (PMOD Technologies). Ho tloha Akkus et al. (2013). Tlhokomeliso: palo le nalane ea eona e hlahisoa hape ka tumello.
Ho hlile ho khothalelitsoe hore mGluR5 downregulation e emetse neuroadaptation e tlatselletsang (Kalivas, 2009), khothalletso ea moputso o susumetsoang ke lithethefatsi (Rutten et al., 2011), kapa ntho e kopanyang litlamorao tsa litaba tse amanang le maemo a arabeloang ka tsela e hlophisitsoeng (Tronci et al., 2010). Setšoantšo 3 e hlahisa mokhoa oa ho se sebetse hantle oa mGluR5 ho lemeng.
Tšoantšiso 3
Setšoantšo sa 3. ho nka karolo mGluR5 ho lemalla.
Joalokaha ho bonoa ho Setšoantšo 3, patlisiso e fetileng e ts'ehetsa mohopolo oa hore mGluR5 e kenya letsoho mehatong e meraro ea bohlokoa ea ho lemalla, ho nts'etsopele le ho fumana thepa, ka boleng ba matlafatso ea lithethefatsi, hammoho le ho oela hape ts'ebelisong. Ho kanna ha etsoa tlhahiso ea hore ts'ebetso e 'ngoe le e' ngoe e hlalosoa ka nepo ke libaka tse fapaneng tsa boko, tse bonts'ang maemo a phahameng a mGluR5 receptor density, mme tse bonts'itsoeng li bonts'a khatello ea methapo ea MGluR5 lipatlisiso tsa rona tsa PET (Deschwanden et al., 2011). Kalivas (2009) o qapile mokhoa o pharaletseng oa bokhoba ba ho lemalla. Sengoli se bontšitse hore ho lemalla ho tsamaisana le ho se sebetse hantle maemong a bohlokoa a potoloho ea boko ea corticostriatal, ho kenyelletsa amygdala, nucleus accumbens (NA), cortex ea pele le motor. Joalokaha re khothaletsa ho Setšoantšo 3, pele ("Karolo e susumetsang"), "cortex ea pele" e ka ba moeli le tšusumetso ea kelello nakong ea methati ea pele ea tlhabollo ea lithethefatsi. Boithuto ba pele-pele ke Chiamulera et al. (2001) e fana ka maikutlo a hore mGluR5 ea hlokahala mohatong ona oa ntlafatso ea bokhoba ka ho kena-kenana le litheko tse ntle tsa lithethefatsi tsa tlhekefetso. Bobeli ("Karolo ea moputso"), Nucleus Accumbens (NA) e bontšitsoe ho susumetsa boleng bo khotsofatsang ba moriana, eseng feela ka dopamine empa hape le ka mosebetsi oa mGluR5 (Bisaga et al., 2008). Ka ho khetheha, ho senyeha ha phetiso ea glutamate lipakeng tsa prelimbic cortex le NA ho fanoe ka maikutlo a hore ho batla lithethefatsi ho thehiloe ka ts'epo e kholo ho boits'oaro bo ithutileng bo amanang le NMDA / mGluR5 receptor system (Kalivas, 2009). Khetlo la boraro ("Karolo e Batlang Bongaka"), lipatlisiso tse ling li ts'ehetsa hore mGluR5 e ameha ho ts'epahalong e kholo ea ts'ebetso ea makoloi - ho fokotsa taolo ea kelello - ka striatum (Kupila et al., 2012). Patlisiso ea rona e phatlalalitsoeng le e sa phatlalatsoang e fana ka maikutlo a hore ho fokotseha ha mGluR5 ho amana le kotsi e eketsehang ea ho khutla ho batho ba tsubang (Akkus, PNAS). Phokotso eo e ka ba pathogenic kapa phetoho e sa lekaneng ea matšeliso. Ha ho kopantsoe hammoho, patlisiso ea morao-rao e bonts'a hore lithethefatsi tse lebisitsoeng mGluR5 li ka ntlafatsa kalafo ea mathata a bokhoba ba methati mefuteng e fapaneng ea kholo ea bona.
Puisano
Bopaki bo shebiloeng bo fana ka maikutlo a ho nka karolo e phahameng ea mGluR5 ka har'a mathata a ho tšoenyeha, OCD, MDD, hammoho le ts'ebetso ea lithethefatsi, le hore kalafo ka mGluRXNNXX e tsebisoang litlhare tsa meriana e ka ba molemo ho batho. Leha ho le joalo, pathožisis ea maikutlo le matšoao a ho tšoenyeha a amanang le OCD e ka fapana le matšoao a ho feto-fetoha le matšoao a ho tšoenyeha a sa amaneng le OCD. Ka lebaka leo, boteng ba matšoao a bonoang ka mokhoa o bonts'ang maikutlo e kanna ea ba ponelopele ea karabelo e potlakileng le e tšoenyang ho lithethefatsi tse lebisitsoeng mGluR5. Ho feta moo, re khothalelitse hore lithethefatsi tse shebileng sisteme ea mGluR5 li ka thusa ho eketsa ho hanyetsa khatello ea maikutlo le ho ntlafatsa likhaello tsa sechaba maemong a khatello ea maikutlo. Kaha khatello ea kahisano ke eona ntho ea bohlokoahali eo e seng ea liphatsa tsa lefutso e bakang khatello ea maikutlo le bofokoli ba sechaba bo hokahane haufi le phokotso ts'ebetsong ea sechaba le boleng ba bophelo, liphetho tsena lipatlisisong tsa liphoofolo li na le bohlokoa bo holimo saenseng le tleliniking.
Haufinyane, National Institute of Mental Health (NIMH) e thehile buka ea nalane, e mabapi le projeke ea thekiso: The Domain Criteria (RDoC). Sena se bonts'oa ts'ebetsong ea NIMH Strategy 1.4 "Ho nts'etsopele sepheo sa ho etsa lipatlisiso, mekhoa e mecha ea ho khetholla mafu a kelello a ipapisitse le maemo a bonoang a boitšoaro le methapo ea kutlo." (http://www.nimh.nih.gov/research-priorities/strategic-objectives/strategic-objective-1.shtml). Bohato bona e bile litholoana tsa ho hlophisa mekhahlelo e thata ea DSM, eo boholo ba eona e ileng ea ntlafatsoa le pele ho lipatlisiso tsa neuroscience (Morris le Cuthbert, 2012). RDoC e hlalosa libaka tse hlano kapa liemahale; Sistimi e mpe ea valence, Sisteme e ntle ea valence, Sistimi ea Cognitive, Sisteme ea lits'ebetso tsa sechaba, lits'ebetso tsa Arousal / taolo. Ho latela bopaki bo shebiloeng mabapi le ho ba le seabo ha mGluR5 ho MDD le OCD, re fana ka tlhahiso ea hore ts'ebetso ea mGluR5 ka kotloloho e amanang le ts'ebetso e mpe ea valence, e kenyelletsang lintlha tse bonts'itsoeng tsa tšabo, ts'oso, ts'okelo e tsitsitseng, tahlehelo, le pherekano e seng. moputso. Kahoo, joalo ka ha lithuto tse hlahlojoang li bontša, kalafo e hanyetsanang le mGluR5 e lokela ho fokotsa matšoao a bonoang. Ntle le moo, re fana ka maikutlo a hore kalafo ea mGluR5 e ka ba molemo ho "mathata a valence" a joalo ka bokhoba le khatello ea maikutlo ka ts'ebetso e sa tloaelehang ea mGluR5 mabapi le sebopeho sa boko le ts'ebetso e amanang le glutamatergic NMDA receptor e amanang le mGluR5 mme e bohlokoa ho kenya letsoho ho ithuteng moputso. . Ka mohlala, Simonyi et al. (2010) e ile ea lekola lithuto tse ngata tsa liphoofolo tse sebelisitseng lisele tsa mGluR5 ho li-knockout ho tseba karolo ea mGluR5 ho ithuta le ho hopola. Ho ithuta ka inhibitory, joalo ka ho ithuta ho qoba ho ithuta, ke mosebetsi o thehiloeng hantle mehlaleng ea liphoofolo o sebelisoang ho ithuta mekhoa ea ho ithuta ea hippocampal, mme o bontšitsoe lithutong tse ngata ho its'etleha holima mGluR5 receptor (Simonyi et al., 2010). Mohlala, lipatlisiso li bonts'itse hyperexpression ea protheine ea mGluR5 ho CA3 nakong ea nako e khuts'oanyane le CA1 nako e telele ea ts'ebeliso ea likhoto (Riedel et al., 2000). Hyman (2005) e hlahisitse mofuta oa tlhaho oa ho lemalla o kenyelletsang mekhoa e sa tloaelehang ea ho ithuta le ho hopola e etsang lintho tsa motheo tsa ho lemalla. Bangoli ba hlahisitse tlhahiso ea tšohanyetso ea nako e telele, e kenyeletsang, liphetoho lipakeng tsa li-receptor tsa glutamate, le taolo ea polelo ea liphatsa tsa lefutso e le mekhoa ea bohlokoa bakeng sa liphetoho tse bakoang ke lithethefatsi tse fumanehang makaleng a sa tloaelehang a amanang le tšebeliso ea lithethefatsi. Kamora nako, lithuto tsa mGluR5 le homeostasis ea ho robala (Hefti et al., 2013; Ahnaou et al., 2015) fana ka maikutlo a karolo ea bohlokoa ea mGluR5 ho li-system tsa tsoho le li-modulatory tsa RDoC.
Figure 4 e akaretsa mekgwa e reriloeng ho buella liketso tsa mGluR5 mathateng a maikutlo le bokhoba ba tahi. Bokaholimo ba Setšoantšo 4 e bonts'a libaka tsa bokaholimo ba mGluR5 bokong; amygdala, hippocampus, striatum, NA, le cortex ea pele. Li-syndromes tsa kelello li lumellana le libaka tseo. ts'ebetso ea mGluR5, e khothalelitsoeng ho amygdala, e kanna ea ba pakeng tsa maikutlo a mantlha a mofuthu, joalo ka matšoenyeho le khatello ea maikutlo. Re hlalositse kamoo litsela tse peli li ka khonehang; Ts'ebetso ea sechaba, le ho ithuta, li ka hokahanya mekhoa e meng. Kahoo, ts'ebetso ea mGluR5 e bontšitse hore e nka karolo ho ithuteng, 'me ka hona, ka ts'ebetso ho hippocampus, NA, le striatum li ka nka karolo mohopolong le moputsong, taolo ea tlhalohanyo le tšusumetso, joalo ka ha li ameha tšebelisong (Sheba le Setšoantšo. 3). Kamora nako, re hlahisitse hore na mGluR5 e ka amana joang le karabelo ea khatello ea maikutlo sechabeng le khaello ea sechaba, e ka bang e loketseng maemo a mangata a kelello. Tafole 2 e fana ka kakaretso ea tikoloho ea ho senyeha ea RDoC, setšoantšo se amanang le kliniki, le karolo ea mGluR5.
Tšoantšiso 4
Setšoantšo sa 4. Kakaretso ea mekhoa ea mGluR5.
TABLE 2
Tafole 2. RDoC le mGluR5.
Litlhaloso tse qetellang
Tlhahlobo ena e hlalositse ho kenya letsoho ha mGluR5 mathateng a ho feto-fetoha ha maikutlo, OCD le bokhoba, 'me ha bo bapisoa le lipatlisiso tsa batho, haholo-holo lipatlisiso tsa PET. Kahoo re bapisa mekhoa e fapaneng ea mekhoa, joalo ka lipatlisiso tsa liphoofolo, MRS, le lithuto tsa PET. Re fana ka maikutlo a hore phello e matla ea ho tšoenyeha e tobileng e tla ba teng haeba kalafo ea antagonistic ea mGluR5 e qalisoa litekong tsa tleliniki ea motho (RDoC). mGluR5 e boetse e tlalehiloe ho FXS, e bonts'itsoeng ke bofokoli ba bohlokoa sechabeng. Ka lebaka leo, ts'ebetso ea mGluR5 e kanna ea se emise feela ts'ebetso e mpe ea lits'ebetso tse mpe tsa valence le lits'ebetso tse khahlisang, empa hape e kenyelletsa ho senyeha lits'ebetsong tsa lits'ebetso tsa maemo a bophelo (RDoC). Sena ke sa bohlokoa haholo tleleniking hobane ho se sebetse hantle ha setjhaba ke sephetho sa bohlokoa sa maemo a bophelo a kelello a kang OCD, khatello ea maikutlo le bokhoba, bo lebisang ho utloeng bohloko bo boholo le litšenyehelo tsa bohlokoa tse sa tobang sechabeng. Mme qetellong, mGluR5 le eona e bonts'itsoe ho ba le karolo e kholo lithahasellong tsa lithethefatsi, ho khothaletsoang hore e bakoe haholo ke ho eketsa boleng ba moputso oa lithethefatsi. MGluR5 ho kenella ho hanyetsaneng ho ka re thusa haholo bakeng sa kalafo ea ho tšoenyeha ka methapo, le ho ntlafatsa boikhathatso ba khatello ea maikutlo sechabeng le ts'ebetsong ea sechaba.
Tlhōlisano ea Tlhaloso
Ngaka Terbeck, Dr Chesterman, le Dr Akkus ha ba na likhohlano tsa thahasello. Ngaka Hasler o amohetse chelete ea lithuso ho tsoa ho Novartis, e hlahisang le ho leka lithethefatsi tse lebisang mGluR5.
References
Abe, T., Sugihara, H., Nawa, H., Shigemoto, R., Mizuno, N., le Nakanishi, S. (1992). Tšobotsi ea molek'hule ea noab metropotic glutamate receptor mGluR5 e kopantsoeng le phetisetso ea pontso ea inositol phosphate / Ca2. J. Biol. CHEM. 267, 13361-13368.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Agid, Y., Buzsáki, G., litaemane, DM, Frackowiak, R., Giedd, J., Girault, J.-A., et al. (2007). Ho sibolloa ha lithethefatsi bakeng sa mafu a kelello ho ka ntlafatsoa joang? Nat. Motsoako oa litheko tsa lithethefatsi. 6, 189-201. Doi: 10.1038 / nrd2217
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Akkus, F., Ametamey, SM, Treyer, V., Burger, C., Johayem, A., Umbricht, D., et al. (2013). Ts'oaetso e tšoaoang ea lefats'e ea mGluR5 receptor e tlamang batho ba tsubang le ba tsubang nakong e fetileng e boletsoeng ke [11C] ABP688 positron emission tomography. Proc. Natl. Acad. Sci. USA. 110, 737-742. Doi: 10.1073 / pnas.1210984110
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Akkus, F., Terbeck, S., Ametamey, SM, Rufer, MD, Treyer, V., Burger, C., et al. (2014). Metabotropic glutamate receptor 5 e tlamang ho bakuli ba nang le bothata bo potelletseng. Int. J. Neuropsychopharmacol. 17, 1915-1922. Doi: 10.1017 / S1461145714000716
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Ametamey, SM, Kessler, LJ, Honer, M., Wyss, MT, Buck, A., Hintermann, S., et al. (2006). Radiosynthesis le tlhahlobo ea preclinical ea11CABP688 joalo ka probe ea ho nahana ka metabotropic glutamate receptor subtype 5. J. Nucl. Moedi. 47, 698-705.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Anderson, JJ, Bradbury, MJ, Giracello, DR, Chapman, DF, Holtz, G., Roppe, J., et al. (2003). Ka vivo receptor ho lula ha bahanyetsi ba mGlu5 ba sebelisang radioligand e ncha [3 H] 3-methoxy-5- (pyridin-2-ylethynyl) pyridine). EUR. J. Pharmacol. 473, 35–40. doi: 10.1016/S0014-2999(03)01935-6
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Ahnaou, A., Raeymaekers, L., Steckler, T., le Drinkenbrug, WHIM (2015). Ho hlahisoa ha metabotropic glutamate receptor (mGluR5) molomong oa potoloho ea boroko ba NREM-REM le homeostasis: bopaki bo tsoang ho litoeba tsa mGluR5 (- / -). Behav. Resin ea Boko. 282, 218-226. Doi: 10.1016 / j.bbr.2015.01.009
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Bear, MF, Huber, KM, le Warren, ST (2004). Khopolo ea mGluR ea ho fokola kelellong ha kelello X. Trends Neurosci. 27, 370-377. Doi: 10.1016 / j.tins.2004.04.009
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Berg, D., Godau, J., Trenkwalder, C., Eggert, K., Csoti, I, Storch, A., et al. (2011). Kalafo ea AFQ056 ea dyskinesias ea levodopa-ikiwa: sephetho sa liteko tsa 2 tse laoloang ka boomo. Tsamaisa. Khahlano. 26, 1243-1250. Doi: 10.1002 / mds.23616
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Berry-Kravis, E., Hessl, D., Coffey, S., Hervey, C., Schneider, A., Yuhas, J., et al. (2009). Lebitso la sefofane le bulehileng, teko e le 'ngoe ea fenobam ho batho ba baholo ba nang le lefu la X. J. Med. Liphatsa tsa lefutso. 46, 266-271. Doi: 10.1136 / jmg.2008.063701
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Bisaga, A., Danysz, W., le Foltin, RW (2008). Ho tsofala ha glutamatergic NMDA le li-mGluR5 receptors li fokotsa ts'ebeliso ea lijo ka mofuta oa mofuta oa mofuta oa mofuta oa ho ja ho itlopa. EUR. Neuropsychopharmacol. 18, 794-802. Doi: 10.1016 / j.euroneuro.2008.05.004
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Boer, K., Encha-Razavi, F., Sinico, M., le Aronica, E. (2010). Phapang e fapaneng ea li-receptors tsa sehlopha sa metabotropic glutamate ho nts'etsapele cortex ea motho. Resin ea Boko. 1324, 24-33. Doi: 10.1016 / j.brainres.2010.02.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Brennan, BP, Rauch, SL, Jensen, JE, le Mopapa, HG (2012). Tlhahlobo e nyarosang ea lithuto tsa maqhubu a khanya ea matla a khoheli. Biol. Psychiatry 73, 31-24. doi: 10.1016 / j.biopsych.2012.06.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Burket, JA, Benson, AD, Tang, AH, le Deutsch, SI (2014). Rapamycin e ntlafatsa boiketlo ba batho ho mofuta oa panya ea BTBR ea likotsi tsa Autism. Brain Res. Bull. 100, 70-75. Doi: 10.1016 / j.brainresbull.2013.11.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Chiamulera, C., Epping-Jordan, MP, Zocchi, A., Marcon, C., Cottiny, C., Tacconi, S., et al. (2001). Ho matlafatsa le litlamorao tse matlafatsang tsa koae ha li eo ho litoeba tsa mouta tse ling. Nat. Neurosci. 4, 873-874. Doi: 10.1038 / nn0901-873
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Chung, W., Choi, SY, Lee, E., Park, H., Kang, J., Park, H., et al. (2015). Liphoso tsa sechaba ho IRSp53 litoeba tsa phetoho e ntlafalitsoeng ke khatello ea NMDAR le mGluR5. Nat. Neurosci. 18, 435-442. Doi: 10.1038 / nn.3927
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Cleva, RM, le Olive, MF (2011). Li-modulators tse sebetsang tsa allosteric tsa mofuta oa 5 metabotropic glutamate receptors (mGluR5) le monyetla oa tsona oa kalafo bakeng sa kalafo ea lits'oaetso tsa CNS. Limolek'hule 16, 2097-2106. Doi: 10.3390 / limolek'hule16032097
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Deschwanden, A., Karolewicz, B., Feyissa, AM, Treyer, V., Ametamey, SM, Johayem, A., et al. (2011). Fokotsa metabotropic glutamate receptor 5 density maemong a maholo a sithabetseng a khethiloeng ke [(11) C] ABP688 PET le thuto ea postmortem. Am. J. Psychiatry 168, 727-734. doi: 10.1176 / appi.ajp.2011.09111607
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Erickson, CA, Mullett, JE, le McDougle, CJ (2009). Memeline ea Open-labeline ho ramatiki ea X e fokolang. J. Autism Dev. Khahlano. 39, 1629-1635. doi: 10.1007 / s10803-009-0807-3
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Erickson, CA, Qalong, M., Stigler, KA, Wink, LK, Mullett, JE, le McDougle, CJ (2011). Phuputso e bulehileng ea tlhaho ea sefofane sa acamprosate ho bacha ba nang le lefu la autistic. J. Ngoana Adolesc. Psychopharmacol. 21, 565-569. Doi: 10.1089 / cap.2011.0034
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pele, MB, le Gibbon, M. (1997). Tataiso ea mosebelisi bakeng sa Puisano e hlophisitsoeng ea Kliniki bakeng sa DSM-IV Axis I Disorders SCID-I: Clinician Version. New York, NY: American Psychiatric Pub.
Feyissa, AM, Chandran, A., Stockmeier, CA, le Karolewicz, B. (2009). Maemo a fokotsehileng a NR2A le NR2B subunits ea NMDA receptor le PSD-95 ka pele ho cortex ea khatello ea maikutlo. Prog. Neuropsychopharmacol. Biol. Psychiatry 33, 70-75. Doi: 10.1016 / j.pnpbp.2008.10.005
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Garber, KB, Visootsak, J., le Warren, ST (2008). Fragile X syndrome. EUR. J. Hum. Liphatsa tsa lefutso. 16, 666-672. Doi: 10.1038 / ejhg.2008.61
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Gass, JT, Osborne, MP, Watson, NL, Brown, JL, le Olive, MF (2009). antGonR5 antagonism e bonts'a methapo ea methamphetamine mme e thibela ho khutlisetsoa ha boitšoaro bo batlang methamphetamine litšoantšong. Neuropsychopharmacology. 34, 820-833. Doi: 10.1038 / npp.2008.140
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Harvey, BH, le Shahid, M. (2012). Metabotropic le ionotropic glutamate receptors joalo ka liphofu tsa neurobiological ho matšoenyeho le mathata a amanang le khatello ea maikutlo: tsepamisa maikutlo ho pharmacology le mehlaleng ea pele ea phetolelo. Pharmacol. Likokoana-hloko. Behav. 100, 775-800. Doi: 10.1016 / j.pbb.2011.06.014
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., LaSalle-Ricci, VH, Ronquillo, JG, Crawley, SA, Cochran, LW, Kazuba, D., et al. (2005). Mats'oao a bonts'ang a ho qobella-ho qobella matšoao a bonts'a likamano tse ikhethileng ho comorbidity ea kelello. Resp Psychiatry. 135, 121-132. Doi: 10.1016 / j.psychres.2005.03.003
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., van der Veen, JW, Tumonis, T., Meyers, N., Shen, J., le Drevets, WC (2007). Fokotsa li-glutamate / glutamine le maemo a γ-aminobutyric acid maemong a sithabetsang a nang le khatello e kholo ea maikutlo a sebelisang proton magnetic resonance spectroscopy. Khoto. Gen. Psychiatry 64, 193-200. doi: 10.1001 / archpsyc.64.2.193
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hasler, G., van der Veen, JW, Geraci, M., Shen, J., Pine, D., le Drevets, WC (2009). Litekanyetso tsa pele tsa cortical gamma-aminobutyric acid pele ho tšenyo ea tšabo e khethiloeng ke proton magnetic resonance spectroscopy. Biol. Psychiatry 65, 273-275. doi: 10.1016 / j.biopsych.2008.06.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hefti, K., Holst, SC, Sovago, J., Bachmann, V., Buck, A., Ametamey, SM, et al. (2013). Ho eketseha ha metabotropic glutamate receptor subtype 5 bokong ba motho kamora bosiu bo le bong ntle le boroko. Biol. Psychiatry 73, 161-168. doi: 10.1016 / j.biopsych.2012.07.030
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hyman, SE (2005). Tlatsetso: bokuli ba ho ithuta le ho hopola. Am. J. Psychiatry 162, 1414-1422. doi: 10.1176 / appi.ajp.162.8.1414
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Hoffpauir, BK, le Gleason, EL (2002). Ho kenya ts'ebetso ea li-modGates tsa mGluR5 moduli tsa GABAA receptor liseleng tse khutlang. J. Neurophysiol. 88, 1766-1776.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Hulka, LM, Treyer, V., Scheidegger, M., Preller, KH, Vonmoos, M., Baumgartner, MR, et al. (2014). Ho tsuba empa ho se ts'ebeliso ea koae ho kopantsoe le "cervine" ea methapo e nyane ea calcam e fumanehang bathong. Mol. Psychiatry 19, 625-632. Doi: 10.1038 / mp.2013.51
Text e feletseng ea CrossRef | Google Setsebi
Kalivas, PW, le Volkow, ND (2005). Motheo oa bokhoba ba ho lemalla: mokhoa oa tšusumetso le khetho. Am. J. Psychiatry 162, 1403-1413. doi: 10.1176 / appi.ajp.162.8.1403
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Kalivas, PW (2009). The glutamate homeostasis hypothesis ea ho lemalla. Nat. Rev. Neurosci. 10, 561-572. Doi: 10.1038 / nrn2515
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Krystal, JH, Mathew, SJ, D'Souza, DC, Garakani, A., Gunduz-Bruce, H., le Charney, DS (2010). Likopo tse ka bang teng tsa mafu a kelello tsa li-agonists tsa metabotropic glutamate receptor le bahanyetsi. Lithethefatsi tsa CNS 24, 669–693. doi: 10.2165/11533230-000000000-00000
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Kupila, J., Kärkkäinen, O., Laukkanen, V., Tupala, E., Tiihonen, J., le Storvik, M. (2012). mGluR1 / 5 li-receptor densities tse bokong ba litaba tsa joala: Phuputso e entsoeng ka likarolo tsohle tsa hemisphere. Resp Psychiatry. 12, 149-155. Doi: 10.1016 / j.pscychresns.2012.04.003
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Koros, E., Rosenbrock, H., Birk, G., Weiss, C., le Sams-Dodd, F. (2007). MGlu5 mokhethi receptor antagonist MTEP, e ts'oanang le bahanyetsi ba li-receptor ba NMDA, e etsa hore ho be le nako ea ho itšehla thajana ka likhoto. Neuropsychopharmacology 32, 562-576. doi: 10.1038 / sj.npp.1301133
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Lea, PM, le Faden, AI (2006). Metabotropic glutamate receptor subtype 5 antagonists MPEP le MTEP. Rev Rev Drug Rev. 12, 149-166. Doi: 10.1111 / j.1527-3458.2006.00149.x
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Legutko, B., Szewczyk, B., Pomierny-Chamioło, L., Nowak, G., le Pilc, A. (2006). Phello ea kalafo ea MPEP ho polelo ea tlhaho ea neurotrophic factor gene. Pharmacol. Rep. 58, 427-430.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Luykx, JJ, Laban, KG, van den Heuvel, MP, Boks, MPM, Mandl, RCW, Kahn, RS, et al. (2012). Karolo ea tikoloho le boemo bo ikhethileng ba glutamate bothateng bo boholo ba khatello ea maikutlo: tlhahlobo ea meta-ea (1) liphumano tsa H-MRS. Neurosci. Biobehav. Tšen. 36, 198-205. Doi: 10.1016 / j.neubiorev.2011.05.014
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Meldrum, BS (2000). Glutamate e le neurotransmitter bokong: tlhahlobo ea physiology le pathology. J. Nutr. 130, 1007.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Morris, SE, le Cuthbert, BN (2012). Tlhahlobo ea Domain ea Patlisiso: Lits'ebetso tsa kelello, li-circuits tsa neural, le boholo ba boitšoaro. Clin ea Dialogues. Neurosci. 14, 29-37.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Olive, MF (2005). Li-receptors tsa mGlu5: neuroanatomy, pharmacology, le karolo ho tlatseng lithethefatsi. Borr. Rev Psychchi Rev. 1, 197-214. Doi: 10.2174 / 1573400054065578
Text e feletseng ea CrossRef | Google Setsebi
Phan, KL, Fitzgerald, DA, Cortese, BM, Seraji-Bozorgzad, N., Tancer, ME, le Moore, GJ (2005). Anterior cingrate neurochemistry ho mathata a ho tšoenyeha ka sechaba: 1H-MRS ho 4 Tesla. Neuroreport 16, 183–186. doi: 10.1097/00001756-200502080-00024
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pittenger, C., Krystal, JH, le Coric, V. (2006). Lithethefatsi tse fanang ka maikutlo a glutamate e le mahlahana a li-pharmacotherapeutic kalafong ea ts'oaetso ea khatello e matla. NeuroRx 3, 69-81. Doi: 10.1016 / j.nurx.2005.12.006
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Pollack, MH, Jensen, JE, Simon, NM, Kaufmann, RE, le Renshaw, PF (2008). Boithuto bo phahameng ba MRS ba GABA, glutamate le glutamine bothateng ba matšoenyeho a sechaba ?: karabelo kalafong e nang levetiracetam. Prog. Neuropsychopharmacol. Biol. Psychiatry 32, 739-743. Doi: 10.1016 / j.pnpbp.2007.11.023
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Riaza Bermudo-Soriano, C., Perez-Rodriguez, MM, Vaquero-Lorenzo, C., le Baca-Garcia, E. (2012). Mehopolo e ncha ho glutamate le matšoenyeho. Pharmacol. Likokoana-hloko. Behav. 100, 752-774. Doi: 10.1016 / j.pbb.2011.04.010
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Riedel, G., Casabona, G., Platt, B., Macphail, EM, le Nicoletti, F. (2000). Tšabo e nang le tšabo ea nako le tlhoko-tlatsetso e ikhethang ea polelo ea mGlu5 ea protein receptor ho rat hippocampus. Neuropharmacology 39, 1943–1951. doi: 10.1016/S0028-3908(00)00037-X
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Rutten, K., De Vry, J., Bruckmann, W., le Tzschentke, TM (2011). Pharmacological blockade kapa "genetic knockout" ea NOP receptor e hlahisa litholoana tse matlafatsang tsa morphine ho likhoto. Lithethefatsi. 114, 253-256. Doi: 10.1016 / j.drugalcdep.2010.10.004
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Romano, C., van den Pol, AN, le O'Malley, KL (1996). Pontšo e ntlafalitsoeng ea nts'etsopele ea metabotropic glutamate receptor mGluR5 bokong ba rat: protheine, mRNA splice variets, le kabo ea libaka. J. Bapisa. Neurol. 367, 403-412.
Rosenberg, DR, le Keshavan, MS (1998). Ho mofuta oa neurodevelopmental oa lefu le lemalloang. Biol. Psychiatry 43, 623–640. doi: 10.1016/S0006-3223(97)00443-5
Text e feletseng ea CrossRef | Google Setsebi
Sanacora, G., Zarate, CA, Krystal, JH, le Manji, HK (2008). Ho shebella tsamaiso ea glutamatergic ho nts'etsopele rialo, kalafo e ntlafalitsoeng bakeng sa mathata a maikutlo. Nat. Motsoako oa litheko tsa lithethefatsi. 7, 426-437. Doi: 10.1038 / nrd2462
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Schoepp, DD (2001). Ho senola mesebetsi ea li-receptors tsa presynaptic metabotropic glutamate tsamaisong ea methapo e bohareng. J. Pharmacol. Hlakola Ther. 299, 12-20.
Li-PubMed Abstract | Tlhaloso e feletseng | Google Setsebi
Segrin, C. (2000). Khaello ea litsebo tsa kahisano e amanang le khatello ea maikutlo. Clin. Psychol. Tšen. 20, 379–403. doi: 10.1016/S0272-7358(98)00104-4
Text e feletseng ea CrossRef | Google Setsebi
Simonyi, A., Schachtman, TR, le Christoffersen, GR (2010). Metabotropic glutamate receptor subtype 5 antagonism ho ithuta le ho hopola. EUR. J. Pharmacol. 639, 17-25. Doi: 10.1016 / j.ejphar.2009.12.039
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Soares, DP, le Molao, M. (2009). Magnetic resonance visroscopy ea boko: tlhahlobo ea metabolites le ts'ebeliso ea bongaka. Clin. Radiol. 64, 12-21. Doi: 10.1016 / j.crad.2008.07.002
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Swanson, CJ, Bures, M., Johnson, MP, Linden, A-M., Monn, JA, le Schoepp, DD (2005). Metabotropic glutamate receptors joalo ka liphofu tse ncha tsa lipelaelo le khatello ea maikutlo. Nat. Motsoako oa litheko tsa lithethefatsi. 4, 131-144. Doi: 10.1038 / nrd1630
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Szeszko, PR, Christian, C., Macmaster, F., Lencz, T., Mirza, Y., Taormina, SP, et al. (2008). Litaba tse fetohileng tsa sebopeho litabeng tsa psychotropic tse nang le khatello ea kelello ea bohlasoa ba bana: thuto e ntlafalitsoeng ea voxel-based morphometry. Am. J. Psychiatry 165, 1299-1307. doi: 10.1176 / appi.ajp.2008.08010033
Text e feletseng ea CrossRef | Google Setsebi
Tatarczyńska, E., Klodzińska, A., Chojnacka-Wójcik, E., Palucha, A., Gasparini, F., Kuhn, R., et al. (2001). Lisosa tse ka 'nang tsa bakoa ke ho tšoenyeha ka maikutlo le litla-morao-morao tsa MPEP, mohanyetsi ea matla le ea sebetsang oa mGlu5 receptor. Br. J. Pharmacol. 132, 1423-1430. Doi: 10.1038 / sj.bjp.0703923
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Tronci, V., Vronskaya, S., Montgomery, N., Mura, D., le Balfour, DJK (2010). Litlamorao tsa mGluR5 receptor antagonist 6-methyl-2- (phenylethynyl) -pyridine (MPEP) mabapi le likarabo tsa boitšoaro ho nicotine. Psychopharmacology 211, 33–42. doi: 10.1007/s00213-010-1868-x
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Van den Heuvel, OA, Remijnse, PL, Mataix-Cols, D., Vrenken, H., Groenewegen, HJ, Uylings, HBM, et al. (2009). Matšoao a ka sehloohong a pherekano e sa bonahaleng e khothalletsoang ke tsamaiso ea methapo e ikhethileng. boko 132, 853-868. Doi: 10.1093 / boko / awn267
Text e feletseng ea CrossRef | Google Setsebi
Wagner, KV, Hartmann, J., Labermaier, C., Häusl, AS, Zhao, G., Harbich, D., et al. (ka khatiso). Mesebetsi ea Homer1 / mGluR5 e kotsing ea ho ba le khatello ea maikutlo ea maemo a bophelo sechabeng. Neuropsychopharmacology. Doi: 10.1038 / npp.2014.308
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Yüksel, C., le Öngür, D. (2010). Magnetic resonance visroscopy lithuto tsa tlhekefetso tse amanang le glutamate mathateng a maikutlo. Biol. Psychiatry 68, 785-794. doi: 10.1016 / j.biopsych.2010.06.016
Text e feletseng ea CrossRef | Google Setsebi
Zarei, M., Mataix-Cols, D., Heyman, mimi, Hough, M., Doherty, J., Burge, L., et al. (2011). Liphetoho tsa bophahamo ba taba ea bohlooho le bosoasoi bo bosoeu ho bacha ba nang le bothata ba ho bona lintho li ba tsamaela hantle. Biol. Psychiatry 70, 1083-1090. doi: 10.1016 / j.biopsych.2011.06.032
Li-PubMed Abstract | Tlhaloso e feletseng | Text e feletseng ea CrossRef | Google Setsebi
Mantsoe a bohlokoa: mGluR5, PET, mathata a maikutlo, ho lemalla, ho tšoenyeha
Caring: Terbeck S, Akkus F, Chesterman LP le Hasler G (2015) Karolo ea metabotropic glutamate receptor 5 ho pathogeneis ea mathata a maikutlo le ho lemalla: ho kopanya bopaki ba preclinical le lithuto tsa motho tsa Positron Emission Tomography (PET). Ka pele. Neurosci. 9: 86. Doi: 10.3389 / fnins.2015.00086
E amohetsoe: 07 Januari 2015; E amohetsoe: 27 February 2015;
E hatisitsoe: 18 March 2015.
E hlophisitsoeng ke:
Ashok Kumar, Univesithi ea Florida, USA
Hlahloba by:
Karthik Bodhinathan, Setsi sa Patlisiso ea Bongaka Sanford Burnham, USA
Amber M. Muehlmann, Univesithi ea Florida, USA
Copyright © 2015 Terbeck, Akkus, Chesterman le Hasler. Ena ke sengoloa se bulehileng se fihletsoeng ka tlase ho License ea Boikarabelo ba Creative Commons (CC BY). Ho sebelisoa, ho abeloa kapa ho hlahisa liforomo tse ling ho lumelloa, hafeela bangoli ba pele kapa ba le lengolo la tumello ba tlotlisoa le hore sengoliloeng sa pele sa makasine ena se boleloa, ho latela mokhoa o amohelehang oa thuto. Ha ho sebelisoe, ho abeloa kapa ho hlahisa ho lumelloa ho sa lumellaneng le melao ena.
* Litaba: Sylvia Terbeck, Sekolo sa Psychology, Setsi sa Bophelo le Saense ea Batho, Univesithi ea Plymouth, PL4 8AA, Plymouth, UK [imeile e sirelelitsoe]
;
