Curr Opin Pharmacol. Sengoloa se ngotsoeng; e fumaneha ho PMC 2013 Oct 7.
E hatisitsoe ka mokhoa o qetelle o hlophisitsoeng e le:
PMCID: PMC3791851
NIHMSID: NIHMS468294
Moetso oa khatiso oa ho qetela oa mohatisi o fumaneha ho Curr Opin Pharmacol
Sheba lihlooho tse ling ho PMC hore Qotsa sehlooho se hatisitsoeng.
inahaneloang
Li-hypocretins (tse khutsufalitsoeng "Hcrts" - tse bitsitsoeng "li-orexins") ke li-neuropeptide tse khethiloeng feela ke palo e nyane ea li-neuron ho hypothalamus ea morao. Li-peptide tsena li tlama li-receptor tse peli tse leng teng bokong bohle ba boko tse amanang le mesebetsi e fapaneng ea kelello le 'mele. Pele, ts'ebetso ea boko Hcrt e fumanoe e e-na le karolo e kholo ho taolo ea phetoho ea boroko / ho tsoha. Boithuto ba morao-rao bo bonts'a li-Hcrts li ka bapala karolo ea mesebetsi e meng ea 'mele, ho kenyelletsa takatso ea lijo, ho lemalla le khatello ea maikutlo. Ha li kopantsoe hammoho, liphuputso tsena li bonts'a karolo e akaretsang bakeng sa li-Hcrts ho arolelanang maikutlo a lerato, haholo ha sebopuoa se tlameha ho arabela likhatellong le mathata a sa lebelloang tikolohong.
Selelekela
E se e le lilemo tse leshome ho tloha ho sibolloa ha li-hypocretins (Hcrts), 'me lilemong tse leshome tse fetileng re ithutile haholo ka polelo, sebopeho le tšebetso ea bona. Nakoana kamora hore ba sibolloe, karolo ea bohlokoa ea li-Hcrts ho boloka tsoho e tlalehiloe mefuta e mengata e kenyeletsang batho [1-5]. Lilemo tse latelang li netefalitse feela bopaki ba hore li-Hcrts li hlokahala ka bobeli ho li hlokomela le ho lekana ho etsa hore motho a hlaphoheloe, 'me hona joale li nkuoa e le "li-priside tse matlafatsang" haholo.6-7]. Morao tjena, li-Hcrts le tsona li bile le tšusumetso mesebetsing ea 'mele le boits'oaro bo bong ntle le ho tsosa. Thutong ena, re fana ka kakaretso ea boko Hcrts le li-receptor tsa bona mme re lekola lithuto tsa morao-rao tse hlahisang karolo ea Hcrts mesebetsing e fapaneng ea 'mele. Ha re leka ho hokahanya lithuto tsena, re fana ka maikutlo a hore mesebetsi e 'meli e akaretsang ea li-Hcrts ke ho kopanya ho falla le ho hlasimoloha ho hoholo.
Hypocretins
Li-Hcrts li fumanoe ka boikemelo ke lihlopha tse peli matsatsing a morao a 1990s [8,9]. Li na le li-peptide tse patiloeng, hypocretin-1 le hypocretin-2 (Hcrt1 le Hcrt2; hape e tsejoa e le "orexin A" le "orexin B", ka ho latellana). Li-peptide tsena li sebetsoa ho tsoa ho mofuta o tšoanang oa "genes", "prrohypocretin" (ppHcrt), 'me li hlahisoa feela sebakeng sa bongoana sa bongoana ba hypothalamic [8,9]. Hctrs le li-receptor tsa bona le tsona li hlahisoa ho periphery [10], empa tlhahlobisong ena re shebisisa Hctrs ea tsamaiso ea methapo e bohareng.
Brain Hcrt neurons e amohela likhakanyo tse tsoang ho li-nuclei tse ngata ho hypothalamus, li -ortortex, claustrum, moeli oa bethe ea stria terminalis, griaqueductal grey, dorsal raphe nucleus, le lateral parabrachial nucleus [11]. Li-neurons tsa Hcrt li fumana ho tsoa ho GABAergic, glutamatergic, le cholinergic neurons [12]. Ho feta moo, a vitro lithuto tsa electrophysiology li bonts'a li-neurotransmitters tse ngata / li-neuromodulators li thabisa li-neurons tsa Hcrt (ho kenyeletsa le corticotropin e lokollang factor, ghrelin, neurotensin, vasopressin, le oxytocin) kapa inhibit Hcrt neurons (ho kenyelletsa serotonin, noradrenalin, dopamine, neuropeptide Y, le leptin [13].
Ka hona, li-neurons tsa Hcrt li hlahisa libaka tse fapaneng tsa tsamaiso ea methapo e kholo, ho kenyelletsa le lipalo tse hlahelletseng ho noradrenergic locus coeruleus (LC), histaminergic tuberomammilary nucleus (TMN), serotoninergic raphe nuclei, dopaminergic ventral tegmental tegmental (VTA), cholinergic pedunculopontine tegmental sebakeng sa (PPT) le sebakeng sa morao sa methapo ea methapo ea methapo (LDT), le "galainergic ventrolateral preoptic nucleus" (VLPO) [14]. Li-neuron tsa Hcrt le tsona li rera ho fapana hantle hohle cortex ea 'mele. Maqhubu ke li-peptide tse thabisang kahoo a nyenyefatsa lits'oants'o tsa bona tse sebetsang [8,9].
Ha li kopantsoe hammoho, lithuto tsena tsa anatomical le electrophysiological li fana ka maikutlo a hore li-neurons tsa Hcrt li kopanya matšoao a fapaneng a homeostatic ho tloha tsamaisong ea methapo ea methapo le methapo, le projeke ho likarolo tse ngata tsa boko, tse ngata li hlalosang li-neuromodulators mme li khona ho laola mesebetsi le boits'oaro bo fapaneng ba mmele.Setšoantšo sa 1).
Li-receptors tsa hypocretin
Li-peptide ka bobeli tsa Hcrt li tlama ka likhakanyo tse fapaneng ho li-receptor tse peli tsa Hcrt, hypocretin receptor 1 (Hcrtr-1-hape e bitsoang "OxR1") le 2 (Hcrtr-2-hape e bitsoang "OxR2")8,9]. Hcrt-r1 e kopanya Hcrt1 ka tumellano e phahameng 'me e tlama Hcrt2 le 100 ho 1000-fold e tlase ho tloaelana [9,15]. Hcrt-r2 e na le tšebelisano e phahameng ho Hcrt1 le Hcrt2 (Setšoantšo sa 2).
Li-receptor tsa Hcrt li fumaneha liteisheneng tsa postynaptic ka mokhoa o ts'oanang le lipakanyo tsa anterogade tsa li-neurocretin neurons tse hlalositsoeng ka holimo (Litšoantšo 1 'me And2) 2) [6,8,9,14]. Hcrt-r1 mRNA e bonoa ka har'a hypothalamus, LC, cortex ea "cerebral" le "brainstem" nuclei. Ka lehlakoreng le leng, Hcrt-r2 mRNA e hlahisoa ka cholinergic nuclei bokong ba sebopeho sa tikoloho ea mokokotlo, le TMN, hammoho le polelo e akaretsang le Hcrt-r1 ho hypothalamus. Bonyane ka lebaka la khaello ea bahanyetsi ba itseng (lebokose 1), hanyane ho tsejoa ka mesebetsi e ikhethileng ea Hcrt-r1 le Hcrt-r2. Leha ho le joalo, liphoofolo tsa Hcrt-r2 tse kokotang, empa eseng litoeba tsa Hcrt-r1, li bonts'a narcolepsy, ka hona li tšehetsa karolo e hlahelletseng bakeng sa receptor ena botsitsong ba bonono.
lebokose 1
Tlhakolo ea meriana le tsamaiso ea Hcrt
Ka lebaka la karolo ea bohlokoa ea li-Hcrts boroko le mathata a mang a amanang le methapo, lik'hamphani tse ngata tsa meriana li lekile ho nts'etsapele basebeletsi ho tsepamisa mokhoa oa Hcrt Ka vivo [49]. Mohanyetsi ea Hcrt ea sebelisoang haholo hangata ka har'a lingoliloeng ke SB-334867 [50]. Mohanyetsi enoa a ka kenella ka mokhoa o hlophisehileng 'me a khutla a thibela Hcrtr-1 binding, leha ho sa hlaka hore na e ama Hcrtr-2 binding. SB-334867 e sebelisitsoe ho tse ngata a vitro lithuto tsa li-neurons tsa Hcrt empa hape le tse fetang 100 + Ka vivo lithuto, ho hlakisa karolo ea Hcrts ka boits'oaro bo bongata ho kenyelletsa takatso ea lijo, boroko, khatello ea maikutlo le bokhoba ba tahi.
Mohanyetsi e mocha oa Hcrt receptor antagonist, ACT-078573 ("Almorexant") [51], e ka tsamaisoa ka molomo, e tšela tšitiso ea mali le mali habonolo, 'me e boele e thibele li-receptor tsa Hcrt ka tumellano e phahameng. Mohlomong ntho ea bohlokoa le ho feta ke hore, litekong tsa pele, motsoako ona ha o hlahise tlhaku (ho sa tsotelehe se ka boleloang ho tloha ho mohanyetsi ea sebetsang ho li-receptor tsa Hcrt ka bobeli), a e etsa tebello e khahlisang ea kalafo ea boroko. Kahoo, mohlomong ACT-078573 e tla ba sehlooho sa ho ithuta haholo nakong e tlang bencheng ea lab le tleliniking.
Hajoale ha ho na li-agonists tse matla tsa Hcrt tse ka sebelisoang Ka vivo ntle le li-peptide tse peli tsa Hcrt ka boeona. Phuputsong ea liphoofolo, li-peptide tsena hangata li kenella ka kotlolloho libakeng tsa boko bo sa sebetseng kapa li kenella ka har'a masapo a methapo ea mali. Leha ho le joalo, ho batho le liphoofolo, li-peptide tsa Hcrt ha li na thuso ha li ente ka mokhoa o hlophisitsoeng [52]. Ka hona, narcolepsy kapa matšoao a cataplexy hangata a phekoloa ho sebelisoa metsoako e lebisang lits'ebetsong tse ling tsa boko. Mohlala, Modafinil e amoheloa ke FDA bakeng sa kalafo ea narcolepsy le mathata a mang a boroko. Motsoako ona o khothatsang mohlomong o thibela phetisetso ea dopamine, empa mohato o nepahetseng oa ts'ebetso ha o tsejoe [52].
Ha re nahana ka likarolo tse sa tsoa sibolloa tsa sistimi ea Hcrt ea ho ja lijo, ho ts'oara moputso, khatello ea maikutlo, ho tepella maikutlo le khatello ea maikutlo, ho hohela kelello ho bolela hore ho qhekella tsamaiso ea Hcrt ho ka ba molemo bakeng sa kalafo ea mafu a kang botena, ts'ebeliso ea lithethefatsi, ho tšoenyeha, ho haelloa ke tlhokomelo, kapa khatello ea maikutlo. Bonyane tse ling tsa likhetho tse ka 'nang tsa e-ba teng tsa kalafo li se li ka etsahala, ha ho fanoa ka nts'etsopele ea bahanyetsi ba phetoho e ncha le e ntlafalitsoeng ea Hcrt e hlalositsoeng ka holimo.
Karolo ea bohlokoa ea li-hypocretins ka botsitso ba motho
Bopaki bo pharaletseng bo bonts'a hore li-Hcrts li khothaletsa le ho boloka ho falimeha, joalo ka ha ho hlalositsoe ka botlalo ho litlhahlobo tse ling tse ntle [6-7,13]. Bopaki bo boholo bo tsoa ho bo fumanoeng ba mantlha ba hore ho senyeha hoa tsamaiso ea Hcrt ho baka bothata ba boroko litabeng tsa litoeba, lintja le batho [1-5]. Boholo ba li-narcoleptics tsa batho li fokotsehile litekanyetso tsa Hcrt ho mokelikeli oa bona oa "cerebrospinal fluid", mme tlhahlobo ea postmortem e senola phokotso ea li-neurons tsa Hcrt ka methapo ea kutlo ea motho ea kelello [4,5]. Ho khahlisang, Sisteme ea Hcrt e boetse e hlokahala bakeng sa ho hlaha ho tloaelehileng ho tsoa ho anesthesia ka kakaretso [16]. Intracerebroventricular (icv) ente ea Hcrt1 le / kapa Hcrt2 e eketsa nako e sebelisitsoeng e falimehile mme e fokotsa nako e sebelisitsoeng ho phallo ea lebelo le ho robala ha REM ka mefuta e fapaneng ea li-vertebrate [17-18]. Ntle le moo, ts'usumetso ea maiketsetso ea li-neuron tsa Hcrt tse sebelisang mocha o sebelisang khanya ea cation, chropsodin-2, e eketsa monyetla oa phetoho ho tloha boroko ho isa ho tsosa nakong ea ho tsitsa le ho lieha ha REM [19]. Kahoo, hona joale ho na le bopaki bo tiileng ba hore li-Hcrts li hlokahala ho boloka le ho lekana ho susumetsa ho falimeha.
Mesebetsi e meng e ka bang teng tsamaisong ea hypocretin
Hcrts e bohlokoa mesebetsing e mengata ea 'mele ntle le ho lula u falimehile. Mohlala, lebitso le leng la Hcrts, "orexins", le ile la khethoa hobane ho kenngoa ha icv Hcrts ho eketsa phepo ea lijo litonong [9]. Liphetho tsena hona joale li nkuoa e le phello e sa laoleheng ea litlamorao tse matlafatsang tsa Hcrts, empa ena e ntse e le sebaka se sebetsang sa lipatlisiso. Microinjection ea Hcrts ka har'a arcuate nucleus e phahamisa li-neuron tsa Orexigenic GABAergic mme e thibela li-neurons tsa POMC tse hlahisang anorexigenic. Hcrts e boetse e thibela li-neuron ka har'a ventothedial hypothalamus, setsi sa satiety se thehiloeng [20]. Kahoo, Hcrts e sebetsa ka mokhoa o iphetetsang ho satiety hormone leptin libakeng tsa bohlokoa tsa home -atic tsa hypothalamus.
Haufinyane, karolo e khahlisang ea Hcrts e thehiloe ho batla meputso le ho lemalla. Ho kenya letsoho ha li-neurons tsa Hcrt ho kopantsoe le mekhoa e amanang le moputso oa lithethefatsi le lijo. Ho hlohlelletsa li-neurons tsa Hcrt kapa microinjection ea Hcrt1 ho VTA kapa li-ventricles li khutlisetsa mekhoa e fetileng e neng e tima lithethefatsi, mme litlamorao tsena li koetsoe ke mohanyetsi oa Hcrtr-1 [21,22]. Lithuto tsena tsa seminal li hlahisitse 'mele oa lipatlisiso o ntseng o hola ka potlako o netefatsang Hcrts moderate process processing [23].
Lintho tse khothatsang le tse ngata li boetse li eketsa khatello ea maikutlo le matšoenyeho. Ka hona, bokhoni ba li-Hcrts ho khothaletsa ho falimeha bo fana ka maikutlo a hore li-peptide tsena li ka bapala karolo ea ho eketsa lits'oants'o tsa khatello ea maikutlo le tsa mmele. Ho ts'ehetsa ts'ebetso ena ea maikutlo, ente ea icv ea Hcrt1 e etsa hore ho be le mekhoa e mengata e amanang le khatello ea maikutlo [17,24]. Ts'ebetso e eketsehileng ea Hcrt e boetse e hokahanngoa le mekhoa e mengata e amanang le khatello ea maikutlo, e kang ho phahama ha methapo ea mali, khatello ea pelo, tšebeliso ea oksijene le mocheso oa 'mele [25-27]. Ho feta moo, likhoele tsa Hcrt li etsa morero oa corticotropin releasing factor (CRF) ka har'a mothapo o moholo oa mali (PVN) [28-29], li-neurons tse etsang hore karabelo ea mokokotlo oa hypothalamus-pituitary-adrenal (HPA) e sebetsane le khatello ea maikutlo. Ts'ebeliso ea bateng ea Hcrt1 elicits depolarization le ho eketsa sekhahla sa spike liseleng tsena tsa CRF [28]. Bopaki bona bo fana ka maikutlo a hore li-Hcrts li ka sebelisana le lits'ebetso tsa CRF tsa mantlha ho kenya letsoho axis ea HPA le lits'ebetso tse ling tse amanang le khatello ea maikutlo.
Ntle le phepelo ea lijo, bokhoba ba khatello ea maikutlo le khatello ea maikutlo, li-Hcrts le tsona li kentsoe mehlaleng ea batho ba sa tsotelleng.30] le boitšoaro ba banna ba botona le botšehali [31]. Hcrts e boetse e tšellelitsoe ho bapala karolo ea matšoao a Lefu la Parkinson [32], schizophrenia [33-34], le khatello ea maikutlo [35-36]. Ka kakaretso lithuto tsa Sisteme ea Hcrt li hatetse pele haholo ho feta moo ho sibolotsoeng ho kenya letsoho ha li-Hcrts borokong le ho tsoha. Lithuto tsena li botsa potso ena: Hcrts e ka bapala karolo ea mofuta o fapaneng joang oa boitšoaro ho tloha ho tsoheng ho fihlela ho ja lijo, ho lemalla, khatello ea maikutlo, ho falimeha, esita le boitšoaro ba thobalano? Ka tlase, re fana ka karabo ea mantlha ea potso ena.
Li-Hypocretins: balaoli ba arousal le allostasis
Karolo ea tsamaiso ea hypocretin ho nts'etsapele ho tsoha hangata e hlalosoa e le karolo ea "ho tsosa." Kameho e akaretsang e tšoauoa ka ts'ebetso e eketsehang ea makoloi le ho eketsa karabelo ho maikutlo le maikutlo a boreleli [37-40]. Seo ho sa khothalletsoeng khafetsa ke hore lits'ebetso tsa ho hlasimoloha ha li kopanele feela ho laoleng lipotoloho tsa boroko / ho tsoha, joalo ka ho falimeha, ho tšoenyeha le matšoao a mafu a mangata a kelello [41]. Habohlokoa le ho feta, sebopeho sa boko se kentse letsoho linthong tse akaretsang tse akaretsang, ho kenyeletsoa sebopeho sa medulla le liponto, "midbrain", "patorsricular"42], amohela likhakanyo tse tsoang ho li-neuron tsa Hcrt. Re fana ka maikutlo a hore haeba li-Hcrts li ka fetola marang-rang ana a monate, ba ka khona ho fetola boits'oaro bo hlophisitsoeng ke marang-rang ana. Ka ho utloisisa karolo eo motho a e phethang e tsebahala ka ho bapala litloaelong tse joalo tse ithutoang kantle ho lebala la boroko, bafuputsi ba ka tseba ho hlahisa lipale tse ntseng li eketseha leha ho le joalo mabapi le ts'ebetso ea li-Hcrts ka boits'oaro bo sa robala. Mohlala, litlaleho tsa morao-rao tse hore Hcrts e fetola boitšoaro ho mefuta ea murine ea khatello ea maikutlo [35-36] ea utloahala ebile ebile e ka lebelloa ha ho shebane le lilemo tse ngata tsa lipatlisiso tsa mafu a kelello tse bonts'ang hore ts'ebetso ea maiketsetso e kenelletse ho batho ba nang le khatello ea maikutlo [43].
Hctrs e bonahala e na le litšusumetso tsa bona tse kholo ha ho hlokahala motho e mong ho laola likhatello tsa mantlha tsa lapeng joalo ka tlala, ho tšoenyeha kapa ho khanna thobalano. Ka hona, re fana ka maikutlo a hore Hcrts e bohlokoa haholo bakeng sa allostasis. Ho fapana le homeostasis, allostasis e boloka botsitso maemong a kantle ho moelelo o tloaelehileng mme e fihlelleha ka ho feto-fetoha ha maikutlo a kahare ho lumellana le litlhoko tse nahannoeng le tse lebelletsoeng tsa tikoloho [44,45]. Mohlala, nahana ka lipatlisiso tsa morao-rao tse lekang litlamorao tsa thibelo ea khalori ka khatello ea maikutlo le khatello ea maikutlo [46]. Mosebetsi o hokahanang le khatello ea maikutlo le khatello ea maikutlo o bonts'a hore litoeba tse tsoang pele tsa "transrohypocretin knockout" le litoeba tse tsoang ho Hcrt li bonts'a karabelo ea khatello ea maikutlo ho khatello ea maikutlo e mpe le e sa foleng [47]. Leha ho le joalo, likarabo tse ling tsa khatello ea maikutlo li bolokehile, ka bobeli ho imeloa kelellong ho bakoang ke tlhahlobo e qobelloang ea ho sesa le khatello ea maikutlo e sa feleng e hlahisoang ke ho hloloa ho sa feleng ha sechaba. Khatello ena ea kelello e baka matšoao a khatello ea maikutlo [46]. Ka mokhoa o khahlisang, tlas'a khatello e matla, Hcrts e ka thibela matšoao a sithabetsang maikutlo, ea khutlisetsa taolo ea "homeostatic" bokong ba kelello. Litoeba tse thibelitsoeng ke khalori li sebetsa hantle teko ea ho sesa e qobelloang (li na le maqhubu a malelele a ho se sebetse hantle le ho se khone ho sebetsa hantle haholo) mme ha li bonts'e liphoso tsa ts'ebelisano ea sechaba ho bapisoa le ad libitum-finyane litoeba. Litoeba tsa Hcrt null ha li bonts'e e 'ngoe ea melemo ena ea thibelo ea khalori. Ho feta moo, palo ea li-neurons tsa c-Fos tse ntle tsa Hcrt tse hlahisoang ke khalori ea thibelo ea khalori e lumellana ka matla le ntlafatso litekong tsa tšebelisano ea sechaba [46]. Sena se fana ka maikutlo a hore li-neurons tsa Hcrt li nka bohato bo fapaneng ba karabelo ea khatello ea maikutlo kholumong e lumellang phoofolo ho hlola matšoao a sithabetsang a bakoang ke khatello ea maikutlo e sa foleng. Ka mokhoa o ts'oanang, le ha li-Hcrts ha li hlile ha li tsose takatso ea lijo tlasa maemo a tloaelehileng, maemong a thibelo ea khalori, Hcrts e hlokahala bakeng sa keketseho e tsitsitseng ea boitšoaro bo lebelletseng ho lijo [48]. Boithuto bona bo boetse bo bontša hore li-neurons tsa Hcrt li boelana le liphetoho tse akaretsang ka boits'oaro, ntlheng ena li netefatsa hore liphoofolo li tla tsoha li be li susumetse ho fumana lijo ka nako e lekanyelitsoeng e fumanehang. Ha ho ntse ho hlokahala lipatlisiso tse ling ho utloisisa mesebetsi ea li-Hcrts ka mefuta e fapaneng ea phephetso ea tikoloho, mehlala ena e bontša hore na mesebetsi ea 'mele ea Hcrts e tla senoloa ka botlalo ha re leboha karolo ea Hctrs ho homeostasis le allostasis.
Nahanisisa
Lilemong tse leshome ho tloha ha ba sibolla, re ithutile ho hongata ka tsamaiso ea boko Hcrt. Ehlile, karolo ea li-Hcrts ho nts'etsopele ho falla ha e khonehe. Tlhahlobo ena e fana ka maikutlo a moralo oa ho nahana ka karolo e akaretsang ea li-Hcrts ka boits'oaro bo bong. Ha ho ntse ho hlokahala lipatlisiso tse ling ho hlakisa tšebetso ea Hcrts hantle, mohlomong karolo ea Hcrt e tla ananeloa ka botlalo molemong oa homeostasis ea sebopeho le allostasis. Ka theknoloji e ncha ea ho nahana le theknoloji ea optogenetic, ntle ho pelaelo lilemo tse leshome tse tlang li tla ba le tsoelo-pele e ntseng e tsoela pele kutloisisong ea sistimi ena e tsotehang ea boko.
lebokose 2
Lipotso tse sa rarolloang mabapi le tsamaiso ea hypocretin
- Na ho na le likarolo tse sebetsang ka har'a Hcrt nuclei? Ho 'nile ha fanoa ka tlhahiso ea hore bonyane ho na le lipalo tse peli tse sebetsang tsa li-neurons tsa Hcrt: baahi ba morao ba bapala karolo ea takatso ea lijo le ho lemalla, le baahi ba litso tse ling ba nkang karolo ho matlafatsong le khatello ea maikutlo [53]. Lithuto tsa nako e tlang lia hlokahala ho leka tšekamelo ena.
- Na li-receptors tsa Hcrt tse peli li laola ka mokhoa o fapaneng mesebetsi ea 'mele le boits'oaro bo fapaneng? Na li hlokahala ka bobeli bakeng sa taolo ea boits'oaro?
- Na li-neuron tsa Hcrt li khothalletsa ho falimeha ka ho bula liwebsaete tse ngata bokong, kapa linthong tse 'maloa tsa bohlokoa tsa li-neuron? Mefuta e 'maloa ea boroko / ho khutla ha mofuta oa boroko, e fana ka maikutlo a hore Hcrt e ntlafatsa boemo ba ho falimeha ka ho fihlella litsing tse ling tsa thabo tse kang LC, TMN, le dorsal raphe nuclei [7]. Leha ho le joalo, liso tsa li-nuclei tsena ha li lebise mofuteng oa matla le ts'epo e tloaelehileng e bolokiloe, leha methapo ena eohle e tlatsitsoe ka phoofolo e le 'ngoe [54]. Kahoo, libaka tsa postynaptic tse hlokahalang ho kenyelletsa tšebetso ea methapo ea kutlo ea Hcrt li ntse li sa hlaka.
- Ke likhatello life tse matlafatsang tse hlokahalang kapa tse lekaneng ho tsamaisa Hcrt-mediated arousal? Likhatello tsa tikoloho li fetolela ts'ebetsong ea Hcrt joang?
lumela hore baa fokola
MEC le JSB ba ts'ehelitsoe ke Lihlahisoa tsa Boithuto ba Boithuto ba Graduate tse tsoang ho National Science Foundation. MEC e boetse e tšehetsoa ke khau ea Ts'ebeletso ea Lipatlisiso tsa Sechaba e tsoang ho Likolo tsa Naha tsa Bophelo. LdL e tšehelitsoe ke lithuso tse tsoang Setsing sa Naha sa Ts'ebeliso e Mpe ea Lithethefatsi, DARPA le NARSAD.
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