Matšoao a Neurotrophics le Mapolanka a Motlakase a Lemalla (2009)

• Neuropharmacology. 2009; 56 (Suppl 1): 73-82.
• E hatisitsoe Inthaneteng 2008 Jul 4. doi:  10.1016 / j.neuropharm.2008.06.059

Scott J. Russo, Michelle S. Mazei-Robison, Jessica L. Ables, 'me Eric J. Nestler^*

Boitsebiso ba Mongoli ► Tlhahisoleseding ea Copyright le License ►

Eya ho:

inahaneloang

1. Selelekela

Karolo ea bohlokoa ea bokhoba ba lithethefatsi ke hore motho o ntse a tsoela pele ho sebelisa lithethefatsi leha a ka tšosoa ka litlamorao tse mpe tsa 'mele kapa tsa kelello. Leha ho sa tsejoe ka bonnete ba hore na ke eng e khannang mekhoa ena ea boits'oaro, ho netefalitsoe hore liphetoho tse etsahalang kahare ho moputso oa boko li bohlokoa (Setšoantšo sa 1). Haholo-holo, liphetoho tsa li-dopaminergic neurons tsa "ventral tegmental area" (VTA) le li-neurons tsa bona tse lebisitsoeng ho li-nucleus accumbens (NAc) ho nahanoa hore li fetola likarabo tsa motho ka mong litokelong tsa lithethefatsi le tsa tlhaho, tse lebisang ho mamellong ea lithethefatsi, ho se sebetse hantle mosebetsing, ho eketseha ha ho ja lithethefatsi, 'me qetellong ho qobelloe tšebeliso (Everitt et al., 2001; Kalivas le O'Brien, 2008; Koob le Le Moal, 2005; Nestler, 2001; Robinson le Kolb, 2004).

 

Setšoantšo sa 1

Mefuta e meholo ea lisele ka har'a ts'ebetso ea methapo ea kutlo

Ho bile le boiteko bo matla lilemong tsa morao tjena ho tseba liphetoho tsa cellular le tsa limolek'hule tse etsahalang nakong ea phetoho ho tloha tšebeliso ea lithethefatsi ea pele ho isa ho tse tlamang. Har'a mefuta e mengata ea liphetoho tse fetotsoeng ke lithethefatsi, ho 'nile ha etsoa tlhahiso ea hore liphetoho ho li-neurotrophic factor (BDNF), kapa li-neurotrophin tse amanang le tsona, le litsela tsa tsona tse tšoaeang li fetola ts'ebetso ea li-neurons ka har'a potoloho ea VTA-NAc le libaka tse ling tsa moputso ho fetolela. khothalletso ea ho sebelisa lithethefatsi (Bolanos le Nestler, 2004; Pierce le Bari, 2001). Taba-kholo ea khopolo-taba ena ke hore liphetoho tse joalo tse bakiloeng ke lisele le limolek'hule li bonts'oa liphetoho tsa morphological tsa li-neurons tse amanang le moputso. Mohlala, tsamaiso e matlafatsang e sa foleng e eketsa ho bokellana ha li-dendrite le palo ea methapo ea dendritic le ho eketsa maemo a BDNF libakeng tse 'maloa tsa moputso oa boko, athe tsamaiso e sa fetoheng ea opiate e fokotseha lekala la dendritic le spine hammoho le maemo a BDNF libakeng tse ling tse tšoanang. hlahlobaRobinson le Kolb, 2004; Thomas et al., 2008). Ho feta moo, morphine e sa foleng e fokotseha boholo ba li-neuron tsa VTA dopamine, phello e khutlisitsoeng ke BDNF (Russo et al., 2007; Sklair-Tavron le al., 1996). Leha ho le joalo, bopaki bo tobileng, bo re qholotsang ba hore liphetoho tsena tsa sebopeho sa moea li ntse li haella.

Tlhahiso ea hore BDNF e kanna ea amana le polasetiki ea sebopeho sa potoloho ea VTA-NAc mefuteng ea ho lemalla e lumellana le lingoliloeng tse kholo tse thathamisitseng ntlha ena ea kholo bakeng sa taolo ea methapo ea methapo. Mohlala, lithuto tse sebelisang ho tlosoa ha tlasa maemo ho BDNF kapa TrkB receptor li bonts'a hore li hlokahala bakeng sa ho eketsoa le ho holofala ha methapo ea methapo ho nts'etsopele ea li-neuron hammoho le ho hlokomela le ho eketsoa ha methapo ea kutlo methapong ea methapo ho ea bokong bohle ba batho ba baholo (Chakravarthy et al., 2006; Danzer et al., 2008; Horch et al., 1999; Tanaka et al., 2008a; von Bohlen Und Halbach et al., 2007).

Le ha methapo e hlakileng ea limolek'hule eo BDNF e kopanyang polasetiki ea moputso oa boko e lulang e sa tsejoe, lithuto tsa morao-rao li bonts'a hore tsela tse tlase tse tlase molemong oa BDNF li fetoloa ka lithethefatsi tsa tlhekefetso, le hore liphetoho tsena tse ts'epahalang tsa "neurotrophic" -Moele oa mehlala ea liphoofolo tse lemalloang ke lithethefatsi. Thutong ena, re tšohla khatelo-pele e ncha kutloisisong ea rona ea hore na li-opiate le li-activates li laola lintlha tsa neurotrophic le litlamorao tsa cellular le boits'oaro tsa litlamorao tsena. Re boetse re fana ka tlhahiso ea libaka tsa lipatlisiso tsa nako e tlang ho sebetsana le litlamorao tse makatsang tsa li-stimulants le opiates ho moronalology ea neuronal le litekanyetso tse itseng tsa boitšoaro tse lumellanang le bokhoba.

2. Lits'oaetso tsa Neurotrophin

Ho sibolla litsela tse bontšang hore nts'etsopele ea neuronal le ho pholoha e bile sepheo sa nako e telele sa lipatlisiso tsa methapo ea kutlo. Leha ho le joalo, neurotrophic factor signature ho system ea methapo ea methapo ea motho e moholo lilemong tse leshome tse fetileng e fetohile sebaka sa bohlokoa sa thahasello, hobane ho supa ha neurotrophic ho bontšitsoe ho fetolela polasetiki ea neural le boits'oaro bophelong bohle ba setho (bakeng sa tlhahlobo ea bona (Chao, 2003)). Ntho ea pele ea neurotrophic e khethiloeng, nerve ukukhula factor (NGF), e qheletsoe ka thoko ho 1954 (Cohen et al., 1954); mofuta oa gene ka boeona ha oa ka oa hlaha ho fihlela 1983 (Scott et al., 1983). Ho sibolloa hona ho ile ha lateloa haufi-ufi ke tlhoekiso le tlhaiso ea lintlha tse ling tsa kholo ea NGF tse hlalosang lelapa la neurotrophin: BDNF (Barde et al., 1982; Leibrock et al., 1989), neurotrophin-3 (NT3) (Hohn et al., 1990; Maisonpierre et al., 1990), le neurotrophin-4 / 5 (NT4 / 5) (Berkemeier et al., 1991). Litho tsa lelapa la Neurotrophin ke li-paralogs mme li arolelana bohlokoa ba li-homology (Hallbook et al., 2006); kaofela ke li-polypeptides tse hlahisang Homodimerize 'me li fumaneha ka mefuta ea boqheku le e holileng ea CNS. Le haesale ho nahanoa hore sebopeho se hlakileng sa 13 kDa e ne e le molek'hule ea sebetsang, lipatlisiso tsa morao tjena li bonts'a hore mefuta ea li-neurotrophin, e bolokang N-terminus ea bona, e bonoa bokong (Fahnestock et al., 2001) le ho buisana ka mela ea li-cascade tse arohaneng le li-peptide tse holileng. Ketso ea NGF ho CNS ea batho ba baholo e fumaneha haholo liseleng tsa cholinergic bokong ba basal, athe ts'ebeliso ea li-neurotrophin tse ling e atile haholo.

Ho hlaka ho eketsehileng ha lets'oao la neurotrophin ho hlahisoa ka polelo e khethollang ea li-receptor tsa neurotrophin, tse ka arohanngoang ka mekha e 'meli, kinoprosin e amanang le tropomyosin-kinase (Trk) le li-receptor tsa P75 neurotrophin (p75NTR). P75NTR e qalile e tsebisoe e le receptor ea NGF (Johnson et al., 1986), empa ha e le hantle e tlama mefuta ea tlhaho le e holileng ea li-neurotrophin tsohle tse 'ne (Lee le al., 2001; Rodriguez-Tebar et al., 1990; Rodriguez-Tebar et al., 1992). Ho fapana le p75NTR, lelapa la Trk la li-receptors le bontša ho khetheha bakeng sa ligands ea eona. Li-receptor tsa TrkA li tlama ka ho khetheha NGF (Kaplan et al., 1991; Klein et al., 1991), reckor ea TrkB e tlama BDNF (Klein et al., 1991) le NT4 / 5 (Berkemeier et al., 1991), le reckor ea TrkC e tlama NT3 (Lamballe et al., 1991). Le ha li-neurotrophin tse holileng li na le tumellano e eketsehang bakeng sa li-receptor tsa Trk ha li bapisoa le li-propeptides, lifomu tse sa emeng le tse holileng li ka tlama p75NTR ka tumellano e phahameng. Ho kenyelletsa moo, p75NTR e bontšitsoe ho theha li-complexes tse nang le Trk receptors, mme li-receptor tsena tsa li-receptor li bonts'a kholo e eketsehang bakeng sa li-ligk tsa Trk tse ikhethileng ha li bapisoa le Homodimeric Trk.

Li-receptor tsa Trk ke liprotheine tse fetang e le 'ngoe tsa transmembrane spanning tse entsoeng ka sebaka se kopanyang sa ligand le extracellular le sebaka se ikhethileng se nang le domain ea tyrosine kinase. Hoa tšoana le tse ling tsa li-receptor tyrosine kinases, li-Trk receptors Homodimerize ka karabelo ea ligand e tlamang, e lumellang trans-phosphorylation kahare ho ts'ebetso ea ts'ebetso ho eketsa ts'ebetso ea matla ea receptor kinase. Trans-phosphorylation libakeng tsa tyrosine ka hara domain ea juxtamembrane le C-terminus e hlahisa libaka tsa sehokelo sa liprotheine tsa SH2 (Src Homology 2) -type "linker", tse kang Src homology domain e nang le liprotheine (Shc), le phospholipase Cγ (PLCγ) ), ka ho latellana. Shc binding e qala mats'oao a tšoaeang liphororo a lebisang qetellong ts'ebetsong ea mitogen-activated protein kinase (MAPK) le phosphatidylinositol 3'-kinase (PI3K) litseleng. Ho hlohlelletsa tsela ea MAPK ho kenyelletsa ts'ebetso ea extracellular ishara-regature kinase (ERK), ha ho tlangoa ha insulin receptor substrate (IRS) ho lebisa ho amoheng le ho kenya ts'ebetsong ha PI3K le ts'ebetsong ea li-kinases tse tlase tse kang thymoma viral proto-oncogene (Akt) , e boetse e tsejoa e le protheine kinase B (PKB). Phosphorylation le ts'ebetso ea PLCγ e lebisa ho thehoeng ha inositol (1,4,5) triphosphate (IP₃) le diacylglycerol (DAG) le ho susumetseng hoa protheine kinase C (PKC) le cellular Ca²⁺ tsela. Litsela tse tharo tse kholo tsa ho saena — PI3K, PLCγ, le MAPK / ERK - e hlahisitsoeng ke ts'ebetso ea Trk receptor li bonts'itsoe ho Setšoantšo sa 2. Ho khahlisang ke hore ho na le bopaki ba ts'ebetso e fapaneng ea ts'ebetso ea likhase tsena tse tharo ho latela neurotrophin, mofuta oa li-receptor, le matla a pontšo le nako e amehang (bona (Segal, 2003). Ts'usumetso e phapang ea litsela tsena tse tlase e bonahala e sebetsa haholo ho liphetoho tse tlisoang ke lithethefatsi ho morphology le boitšoaro, joalo ka ha ho tla hlakisoa likarolo tse latelang tsa tlhahlobo ena.

 

Setšoantšo sa 2

Lits'oaetso tsa "Intracellular" tse bontšang tsela e kenang nokeng ea li-neurotrophin

Ha ho bapisoa tsebo e pharalletseng ea litlamorao tsa ts'ebetso ea receptor ea Trk, ha ho tsejoe hakaalo ka karolo ea ho saena ha p75NTR ts'ebetsong ea neurotrophin. Ts'ebetso ea li-activists tsa Trk hangata e lebisa ho matsatsing a ho pholoha le ho khethollo, athe ts'ebetso ea p75NTR e qala ts'ebetso ea ho pholoha le pro-lefu la ho supa lefu. Pholoha e tšoaeang p75NTR e hloka ho theoha hoa Nuclear Factor kappa B (NFκB) eo ho nahanoang hore e qaptjoa ka tsela e sa tobang ka TNF (tumor necrosis factor) e amanang le receptor-factor factor 4 / 6 (TRAF4 / 6) kapa receptor e kenang protheine ea 2 (RIP). hlahlobaChao, 2003)). Le ha ho saena ka neurotrophin ho lumella mefuta e mengata e rarahaneng ea lipontšo tse itšetlehileng ka sebopeho sa polelo sa li-neurotrophin le li-receptor le ts'ebetso ea li-peptide tsa neurotrophin, tlhahlobo ena e shebile ka liphetoho tse tlisoang ke lithethefatsi tseleng e emisang methapo ea methapo ea kutlo ea neurotrophin.

3. Liphetoho tse hlahisitsoeng ke lithethefatsi ho BDNF libakeng tsa moputso oa boko

Liphetoho maemong a protheine ea BDNF le mRNA li se li hlahlobiloe libakeng tse ngata tsa boko kamora ho tsamaisoa ha lihlopha tse ngata tsa lintho tse lemalloang. Li-stimulants li hlahisa phallo e pharalletseng, empa e le ea nakoana, e kenella ea protheine ea BDNF ho NAc, prefrontal cortex (PFC), VTA, le khubu ea bohareng (CeA) le basolateral (BLA) nuclei ea amygdala (Graham et al., 2007; Grimm et al., 2003; Le Foll et al., 2005). Ka bobeli likhohlano le tse sa tsekisanang (ke hore, liphoofolo tse tlameletsoeng ho liphoofolo tse iphehlang) Tsamaiso ea koae e baka maemo a phahameng a protheine ea BDNF ho NAc (Graham et al., 2007; Liu et al., 2006; Zhang et al., 2002). Ka mokhoa o ts'oanang, ho tlosoa ha nako e telele ho fihlela matsatsing a 90 kamora ho iphelisa ha koae ho kopantsoe le protheine ea BDNF e kholo ho NAc, VTA, le amygdala (Grimm et al., 2003; Pu et al., 2006), mme ho na le bopaki ba pejana ba hore kemiso ea epigenetic ho bdnf gene e kanna ea kenella ho kenella ts'ebetsong ena e phehellang (Kumar et al., 2005).

Le ha ho entsoe liphuputso tse fokolang ho hlahloba maemo a BDNF mRNA le liprotheine kamora ho pepesetsoa li-opiate, ho bonahala eka maemo a BDNF a laoloa ke li-opiate libakeng tse ling tsa boko tse amanang le moputso. Ts'ebetso ea morphine e mpe haholo e eketsa maemo a BDNF mRNA ho NAc, medial PFC (mPFC), VTA, le orbitofrontal cortex. Ho VTA, morphine e sa foleng, e fanoeng ka masela a subcutaneous (sc), ho tlalehoa hore ha e na thuso ho fetoleng polelo ea BDNF mRNA (Numan et al., 1998). Sena, leha ho le joalo, se fapane le liphetoho liprotheine tsa BDNF tse bonoang kamora kalafo ea morphine e sa foleng. Ho sebelisa tekanyetso e ntseng e phahama ea morphine oa intraperitoneal (ip), ho bontšitsoe hore palo ea lisele tsa mmele tsa BDNF tse sa sebetseng ho VTA e fokotsehile (Chu et al., 2007), ho fana ka tlhahiso ea ho fokotsoa hoa tšebetso ea BDNF. Le ha ho se na litlaleho tse hlokometseng polelo ea BDNF ho hippocampus kapa caudate-putamen (CPu) kamora ts'ebetso ea li-activists kapa opiates, lithuto tse joalo li netefalitsoe kaha liphetoho tse matla tsa morphological li hlokometsoe ho "pyramidal neurons" ea "hippocampal CA3" ea sebaka sa hippocampal CAXNUMX le li-spiny neurons tse mahareng (MSNs) ea CPu tlasa maemo ana ((Robinson le Kolb, 2004); bona Lethathamo 1).

 

Lethathamo 1

Liphetoho tsa morphology tse tsamaisanang le lithethefatsi

4. Liphetoho tse bakoang ke lithethefatsi ho BDNF tse bontšang tsela libakeng tse lefuang ka bokong

Liprotheine tse 'maloa tsa li-cascade tsa "neurotrophin" li bontšitsoe hore li laoloa kahare ho sistamine ea mesolimbic dopamine ke li-opiates le li-stimulants; Tsena li kenyelletsa litlamorao tsa lithethefatsi ho IRS-PI3K-Akt, PLCγ, Ras-ERK, le signaling ea NF VerB (Setšoantšo sa 3). Li-stimulants li eketsa phosphorylation ea ERK haholo libakeng tse ngata tsa boko, ho kenyeletsoa NAc, VTA, le PFC, kamora ts'ebetso ea lithethefatsi tse mpe kapa tse sa foleng (Jenab et al., 2005; Shi le McGinty, 2006, 2007; Letsatsi le al., 2007; Valjent et al., 2004; Valjent et al., 2005). Liphumano tsena li tsamaellana le keketseho e susumetsang ea makala a neuronal le palo ea lesapo la mokokotlo, ha re fuoa karolo e thehiloeng ke Ras-ERK ts'ebetsong ea methapo ea methapo. Litlamorao tsa opiates mabapi le ho saena hoa ERK ha li hlake hantle. Haufinyane, ho tlalehiloe hore phosphorylation ea ERK e fokotsehile ho NAc (Muller le Unterwald, 2004), PFC (Ferrer-Alcon et al., 2004), le VTA (liphatlalatso tse sa phatlalatsoang) kamora morphine e sa foleng, phello e lumellanang le lekala le fokotsehileng la neurite le bonoang libakeng tsena ho liphoofolo tse itšetlehileng ka morphine. Leha ho le joalo, mosebetsi oa pejana ho tsoa sehlopheng sa rona mme ba bang ba tlaleha ts'ebetso ea ERK e eketsehang, ho kenyelletsa le phallo ea phosphorylation ea ERK le ts'ebetso ea maiketsetso, ho VTA kamora ho ferekana morphine (Berhow et al., 1996b; Liu et al., 2007; Ortiz et al., 1995). Ho hlokahala lithuto tse ling hape ho fumana hore na liphetho tsena tse sa nepahalang ke life. Ho feta moo, ho bohlokoa ho sebelisa mekhoa e mengata ho lekanya ts'ebetso ea protheine e le hore liketsahalo tsa biochemical li ka tsamaellana le morphological le boits'oaro bo botle. Mohlala, thibelo ea ERK ho VTA dopamine neurons ha e ame boholo ba sele (Russo et al., 2007), joalo ka hore lithuto tsa nako e tlang li hlokahala ho sebetsana le bohlokoa bo sebetsang ba liphetoho tse tlisoang ke lithethefatsi mesebetsing ea ERK sebakeng sena le likarolong tse ling tsa boko kaha li amana le phenotypes tse lemalloang.

 

Setšoantšo sa 3

Liphetoho ho BDNF li-cascades tse bonts'ang li amanang le polasetiki ea opiate le e susumetsang e khothalelitsoeng tsamaisong ea VTA-NAc

Litlaleho tse 'maloa tsa morao tjena li bonts'itse hore IRS-PI3K-Akt signaling e susumetsoa ke lithethefatsi tsa tlhekefetso (Brami-Cherrier et al., 2002; McGinty et al., 2008; Muller le Unterwald, 2004; Russo et al., 2007; Shi le McGinty, 2007; Wei et al., 2007; Williams et al., 2007). Tsamaiso ea opiate e sa foleng e fokotseha phosphorylation ea Akt ka bobeli ho NAc le VTA (Muller le Unterwald, 2004; Russo et al., 2007). Liphetoho tsena tsa biochemical li tsamaisana le ho fokotseha ha methapo ea methapo le khatello ea methapo ea methapo kapa, maemong a VTA dopamine neurons, ho fokolitse boholo ba sele ea mmele (Diana et al., 2006; Robinson et al., 2002; Robinson le Kolb, 1999b; Russo et al., 2007; Spiga et al., 2005; Spiga et al., 2003)

Litlamorao tsa li-stimulants ho IRS-PI3K-Akt ho supa libakeng tsena ha li hlake hantle. Mohlala, cocaine e sa foleng e eketsa ts'ebetso ea PI3K khetla ea NAc mme e fokotsa ts'ebetso ea eona ho mantlha ea NAc (Zhang et al., 2006). Lintlha tsena li tsamaellana le tlaleho ea pejana e bonts'ang hore li-cocaine tse sa foleng li ile tsa eketsa maemo a BDNF mRNA ka har'a khetla ea NAc mme tsa fokotsa le receptor mRNA ea TrKB moleng oa NAc (Filip et al., 2006). Ka hona, liphapang tsa mantlha le tsa mantlha tšebetsong ea PI3K li ka hlalosoa ka molao o fapaneng oa taolo ea BDNF le TrKB ke koae. Hoa thahasellisa hore ha ho sebelisoa mokhoa o akaretsang oa "striatum" (ho kenyeletsoa NAc le CPu), ho bontšitsoe hore amphetamine e fokotsa ts'ebetso ea Akt litokisetsong tsa synaptosome (Wei et al., 2007; Williams et al., 2007), mme re hlokometse litlamorao tse tšoanang tsa cocaine e sa foleng ho NAc ntle le ho khetholla pakeng tsa mantlha le khetla (Pulipparacharuvil et al., 2008). Ntle le moo, lithuto tsena li thatafalloa ke lithuto tsa nako tse sebelisitsoeng ho ithuta liphetoho tsa Akt, hobane mosebetsi oa moraorao oa McGinty le basebetsi mmoho o supa hore amphetamine e sa feleng e baka phetoho ea nakoana le ea nyutlelie ho phosphorylation ea Akt ho striatum (McGinty et al., 2008). Nakong ea pele ea nako ka mor'a taolo ea amphetamine ho na le keketseho e ikhethileng ea Akt phosphorylation, leha ho le joalo, kamora ho qeta lihora tse peli Akt phosphorylation e fokotsehile, ho fana ka maikutlo a hore moano oa puseletso oa ho emisa ketso ena o sebetsa. Ho utloisisa kamano e matla lipakeng tsa li-stimulants le Akt ho saena ho tla ba bohlokoa ho tseba hore na tsela ena e tšoaeang e tsamaisa tšebetso ea polasetiki e tataisang NAc, joalo ka boemo ba opiates ho VTA (bona Karolo ea 6).

Liphetoho ho PLC sign le NF VerB litseleng tse sebelisang tšebeliso e mpe ea lithethefatsi ha li so ithute hantle joalo ka ERK le Akt; leha ho le joalo, mosebetsi oa morao-rao o bonts'a hore litsela tseo ka bobeli li laoloa ke lithethefatsi tsa tlhekefetso. Tsamaiso e sa feleng ea morphine e eketsa palo ea protheine ea PLCγ hammoho le maemo a mofuta oa eona oa ts'ebetso ea tyrosine-phosphorylated (Wolf le al., 2007; Wolf le al., 1999). Ntle le moo, ho ata ha khatello ea bongata ba vaerase ea VC ho VTA ho fumanoe ho eketsa ts'ebetso ea ERK sebakeng sena sa boko (Wolf le al., 2007), ka tsela eo re etsisa keketseho e ts'oanang ea ts'ebetso ea ERK e bonoang kamora morphine e sa foleng lithutong tsa pejana (Berhow et al., 1996b). PLCxp overexpression ho VTA e boetse e laola moputso oa opiate le boits'oaro bo amanang le maikutlo, ka litlamorao tse fapaneng tse bonoang ho rostral vs. caudal VTA (Bolanos et al., 2003). Ka mokhoa o ts'oanang, Graham le basebetsi-'moho (Graham et al., 2007) e hlokometse phosphorylation e ngata ea PLCγ ho NAc kamora ho kula ho sa feleng, joko e sa foleng, le cocaine e sa foleng, phello e neng e itšetlehile ka BDNF.

Boithuto ba pejana ho tsoa sehlopheng sa rona bo bonts'itse hore NF VerB e tsamaisa p105, p65, le IalonB li eketsehile ho NAc ho arabela taolong e sa foleng ea koae (Ang et al., 2001). Sena se lumellana le seo ba se fumaneng ho Cadet le basebetsi-'moho (Asanuma le Cadet, 1998), ea bonts'itseng hore methamphetamine e etsa mosebetsi o tlamang oa NF VerB libakeng tsa litereke. Ha ho nahanoa hore liprotheine tse ling tse laoloang ke lithethefatsi tsa NF VerB li kenya ts'oaetso ea NF VerB, athe tse ling li e thibela, ho ne ho sa hlaka lithutong tsena tsa pele hore na liphetoho tsa protheine tse bonoang li bonts'a keketseho kapa ho fokotseha ha ho boleloa ke NF VerB. Re sa tsoa rarolla potso ena ka ho bonts'a hore taolo e sa foleng ea koae e hatisa mosebetsi oa ho ngolisa oa NF VerB ho NAc, e ipapisitse le liphetho tsa litoeba tsa mokoetlisi oa NF VerB-LacZ (Russo, Soc. Neurosci. Abstr. 611.5, 2007). Bopaki ba morao-rao bo bile le tšusumetso e tobileng ho kenngoeng hoa matšoao a NF VerB ho NAc lithutong le litlamorao tsa cocaine (bona Karolo ea 6). Liphumano tsena tsa pele li a makatsa ebile li netefatsa ho phenyekolla ho kenyeletsa le tlhahlobo ea phello ea li-opiates ho NFalingB ho supa libakeng tsa moputso oa boko.

5. Ts'ebeliso ea "lithethefatsi" e susumetsoang ke lithethefatsi libakeng tsa moputso oa boko

Karolo ea moputso oa boko e bile teng ho tsamaisa lisebelisoa tsa motho ho fumana moputso oa tlhaho, empa sisteme ena e ka silafatsoa kapa ea utsuoa ke lithethefatsi tsa tlhekefetso. Ka har'a potoloho ena, polasetiki ea sebopeho e hangata e tšoauoa ka ho feto-fetoha ha dendrite branching kapa arborization le liphetoho ka bongata kapa morphometry ea spendritic spines. Le ha boits'oaro bo ikhethileng ba boits'oaro bo itšetlehileng ka morphological bo ntse bo ntse bo tsoela pele ho etsoa lipatlisiso, ho lumeloa hore ts'ebetso ea synaptic ha e supe feela ka palo, empa le boholo le sebopeho sa hlooho ea mokokotlo ka mong. Ha e le methapo ea kutlo, e romela likarolo tse tšesaane tse emeng ka makhapetla, multisynaptic, filopodial, kapa makala a makala (bakeng sa tlhahlobo ea bona (Bourne le Harris, 2007; Tada le Sheng, 2006). Ka bokong ba batho ba baholo, tlasa maemo a basal, ho hakanngoa hore bonyane 10% ea methapo e na le libopeho tsena tse bontšang hore polasetiki ke ntho e tsoelang pele bophelo bohle (Fiala et al., 2002; Harris, 1999; Harris et al., 1992; Peters le Kaiserman-Abramof, 1970). Meaho ena e nka nako e telele ebile e ka ba teng ka nako ea lihora tse ts'oaroang le ho phehella halelele ka matsatsi a 'maloa ho vivo (Holtmaat et al., 2005; Majewska et al., 2006; Zuo et al., 2005).

Ho lumeloa hore botsitso ba mokokotaba o sa tsitsang, o sa emeng ho ea sebakeng se tšoarellang, o sebetsang o hlaha ka ts'ebetso e itšetlehileng ka mosebetsi (bakeng sa tlhahlobo ea bona (Tada le Sheng, 2006). Liprotheine tsa tšusumetso tse khothalletsang khatello ea maikutlo ea nako e telele (LTD) li amahanngoa le shrinkage kapa ho khutlisoa ha spine ho li-neurons tsa hippocampal le cortical pyramidal (Nagerl et al., 2004; Okamoto et al., 2004; Zhou et al., 2004), athe ts'ebetso ea ts'ebetso ea nako e telele ea potentiation (LTP) e amana le ho etsoa ha methapo e mecha le keketseho ea methapo e teng (Matsuzaki et al., 2004; Nagerl et al., 2004; Okamoto et al., 2004). Boemong ba limolek'hule, ho lumeloa hore LTP le LTD li qala liphetoho tseleng ea ho tšoaea, le ho kopanngoeng le liprotheine, tseo qetellong li fetolang polymerization ea Actin ho ama lesapo la mokokotlo le botsitso mme qetellong e hlahise lesapo la mokokotlo (PDP) le sebetsang. kapa ho hlakoloa ha lesapo la mokokotlo (LTD) bakeng sa tlhatlhobo bona (Bourne le Harris, 2007; Tada le Sheng, 2006). Kamora botsitso, methapo e fetoha sebopeho sa li-mushroom, e be le methapo e meholoanyane ea li-postynaptic (Harris et al., 1992), mme ho bontšitsoe hore e phehella likhoeli tse ngata (Holtmaat et al., 2005; Zuo et al., 2005). Liphetoho tsena li bonts'a ketsahalo ea cellular e tsitsitseng haholo eo e ka bang tlhaloso e utloahala bakeng sa bonyane liphetoho tse ling tsa boitšoaro bo bolelele bo amanang le bokhoba ba lithethefatsi.

Boholo ba lihlopha tsa lintho tse lemalloang, ha li fanoa ka mokhoa o sa tsitsang, li fetola polasetiki ka har'a potoloho ea moputso oa boko. Boholo ba lithuto tsena li lumellana ebile li amahanya liphetoho tsa sebopeho libakeng tse itseng tsa boko ka boits'oaro bo bontšang ho lemalla. Lilemong tse leshome tse fetileng, Robinson le basebetsi mmoho ba etelletse pele tsela ea ho utloisisa hore na lithethefatsi tsa tlhekefetso li laola polasetiki e hlophisitsoeng joang (bakeng sa tlhahlobo ea bona (Robinson le Kolb, 2004). Ho tloha liphatlalatsong tsena tsa pele, bafuputsi ba bang ba tlhekefetso ea lithethefatsi ba ekelitse ho lingoliloeng tsena tse ntseng li hola ho senola litlamorao tse ikhethang tsa sehlopha sa lithethefatsi ho morphology ea neuronal. Joalokaha ho bontšoa ka Lethathamo 1 'me Setšoantšo sa 3, opiates le li-stimulants li ama ka mokhoa o fapaneng sebopeho sa polasetiki. Li-Opiates li bontšitsoe hore li fokotsa palo le ho rarahana ha li-dendritic spine ho NAc MSNs le mPFC le hippocampus pyramidal neurons, le ho fokotseha boholo ba soma ka kakaretso ba li-neurons tsa VTA dopaminergic, ntle le phello e bonoang ho li-neurons tse se nang dopaminergic sebakeng sena sa boko (Nestler, 1992; Robinson le Kolb, 2004; Russo et al., 2007; Sklair-Tavron le al., 1996). Ho fihla joale, ho na le mokhelo o le mong ho tse fumanoeng, moo ho tlalehiloeng hore morphine e eketsa palo ea lesapo la mokokotlo ho orbitof Pambal cortical neurons (Robinson et al., 2002). Ho fapana le opiates, li-stimulants tse kang amphetamine le cocaine li bonts'itsoe ho eketsa maemo a dendritic le ho rarahana ho NAc MSNs, VTA dopaminergic neurons, le PFC pyramidal neurons, ntle le litlaleho tsa "proteinity" e fokotsehileng ea sebopeho.Lee le al., 2006; Norrholm et al., 2003; Robinson et al., 2001; Robinson le Kolb, 1997, 1999a; Sarti et al., 2007).

Le ha lits'ebetso tsa limolek'hule tse tlase molemong oa li-neurotrophic factor tse neng li sa fetole liphetoho tse sa utloisiseng, tse ngata tsa liphetoho tsena li tsamaisana le liphetoho maemong kapa tšebetsong ea liprotheine tse tsebahalang ka ho laola cyonal cytoskeleton. Tsena li kenyelletsa, empa ha li felle ho, liphetoho tse susumetsoang ke lithethefatsi ho protheine e amanang le microtubule 2 (MAP2), liprotheine tsa neurofilament, protheine e amanang le cytoskeletal e amanang le tšebetso (Arc), LIM-kinase (LIMK), myocyte enhancer factor 2 (MEF2) , cyclin-based kinase s5 (Cdk5) ,ensynaptic density 95 (PSD95), le cofilin, hammoho le liphetoho ho actin cycling, NAc kapa libakeng tse ling tsa moputso oa boko (Beitner-Johnson et al., 1992; Bibb et al., 2001; Chase et al., 2007; Marie-Claire et al., 2004; Pulipparacharuvil et al., 2008; Toda et al., 2006; Yao et al., 2004; Ziolkowska et al., 2005). Kaha liphetoho tse ngata tsa biochemical tse susumetsoang ke li-susumetsang le morphine li ts'oana, ho tla ba bohlokoa ho khetholla lipheo tsa gene tse fapaneng tsa "opiate-" le "stimulant" tse amanang le ts'ebetso ea dendritic, kaha li ka fana ka leseli mabapi le litlamorao tse atamelaneng le opiate le liakatso tsa neurotrophic elemental-itšetleha ka polasetiki sebopeho.

Liphetoho tse fapaneng tsa morphological tse hlahisitsoeng libakeng tsa moputso oa boko ka li-opiates le li-stimulants lia makatsa kaha lithethefatsi tsena tse peli li baka mokhoa o ts'oanang oa boits'oaro. Mohlala, mefuta e khethehileng ea kalafo ea li-opiate le li-stimulants, tseo ka bobeli li hlahisang maikutlo a locomotor le mekhoa e ts'oanang ea ho eketseha ha taolo ea lithethefatsi, e baka liphetoho tse fapaneng khokahanong ea methapo ea methapo ho NAc (Robinson le Kolb, 2004). Kahoo, haeba liphetoho tsena tsa morphological e le babuelli ba bokhoba ba litabatabelo, e kanna ea ba le thepa ea ho batla, eo ka eona phetoho ea mantlha ka mekhoa ka bobeli e hlahisang mokhoa o ts'oanang oa boitsoaro, kapa ba arolelanang boits'oaro bo fapaneng kapa bo bong bo sa sebetseng ka lisebelisoa tsa liteko tse sebelisitsoeng. . Ntle le moo, liphumano tsena li tlameha ho shejoa maemong a taolo ea lithethefatsi ho buuoang ka tsona. Ka mohlala, lithutong tsa rona, liphoofolo li fumana tekanyetso e phahameng ea "subcutaneous morphine", e tsoelang pele e tsoa liphatseng tsa pellet, paradigm e lumellanang haholoanyane le mamello le ts'epo. Ho fapana le hoo, lipapatso tse matlafatsang tse ngata li sebelisa liente ka makhetlo a 'maloa ka sethethefatsi, li lumella maemo a mali hore a be sehlohlolong ebe a khutlela sethaleng pele ho ts'ebetso e latelang. Meetso ea ts'ebeliso ea opiate le e susumetsang ea batho e ka fapana haholo ho tloha ho motho ho ea ho batho. Ka hona, lithuto tsa nakong e tlang li tla hloka ho sebetsana le boits'oaro bo amanang le liphetoho tsa boitšoaro bo khothalletsoang ke lithethefatsi libakeng tsa moputso oa boko moelelong oa litekanyetso le litlamorao tsa taolo ea lithethefatsi tse pepesitsoeng ke seipone sa batho.

6. Karolo ea BDNF le li-cascades tsa eona tse saenneng lipapatsong tse susumetsoang ke lithethefatsi le boits'oaro

Liphetoho linthong tse bonts'ang kholo ea kholo ea kholo ea maemo a hokahanyang li nkoa e le sesosa se ka sehloohong se susumetsang polasetiki ea sebopeho le boits'oaro bo amanang le bokhoba ba lithethefatsi. Lithuto tsa batho li na le meeli. Liphetoho tse bakoang ke lithethefatsi serum BDNF li bonoe bathong ba lemaletseng koae, amphetamine, joala kapa opiates (Angelucci et al., 2007; Janak et al., 2006; Kim et al., 2005), leha ho le joalo mohloli oa BDNF ena, le bohlokoa ba liphetoho tsena ho qalisong le ho lokiseng tlhekefetso li ntse li sa hlaka. E ka ba ho khahlisang lithutong tsa nakong e tlang ho hlahloba BDNF le litsela tsa eona tse tšoaeang likoteng tsa boko ba motho ea postmortem.

Lilemong tse leshome tse fetileng, mosebetsi oa litoeba o thehile tšusumetso ea BDNF maemong a fapaneng a ts'ebetso ea bokhoba. Boithuto ba pele bo bonts'itse hore ts'oaetso ea lehae ea BDNF ho VTA kapa NAc augments locomotor le likarabo tse khahlisang tsa koae, ha tahlehelo ea lefats'e ea BDNF e hlahisa litlamorao tse fapaneng (Hall et al., 2003; Horger et al., 1999; Lu et al., 2004). Mosebetsi oa morao-rao o bontšitse hore ho itaola ka koae ho eketsa ho supa BDNF ho NAc (Graham et al., 2007). Ntle le moo, ts'ebetso e kenelletseng ea NAD ea BDNF e ka itlhompha ka koae le ho batla koae le ho oela hape, ha e ntse e kenella ka antibodies khahlanong le BDNF bdnf gene ho NAc (e fumanoe ka polelo ea bongata ba kokoana-hloko ea Cre recominase ka litoeba tsa BDNF), e thibela boitšoaro bona. Ho ipapisitsoe le lithuto tsena, Graham le basebetsi-'moho (2007) o ile a etsa qeto ea hore tokollo ea BDNF ho NAc nakong ea ts'ebetso ea ts'ebetso ea koae ke karolo ea bohlokoa ea ts'ebetso ea ho lemalla.

Lintlha tsena li tšehetsa pono ea hore BDNF ke molek'hule ea ho khetha liphetoho lipakeng tsa li-neuron tsa NAc tse hlahisoang ke ho pepesehela koae kapa tse ling tse matlafatsang. Ho ea ka tšibollo ena, keketseho e susumetsoang ke BDNF ho supa ho NAc e tla baka keketseho ea maikutlo a methapo ea methapo ea methapo ea methapo ea kutlo, e tla hlakisa likarabo tsa boits'oaro ho li-stimulants hammoho le mehopolo e matla e amanang le lithethefatsi e bohlokoa bakeng sa ho khutla le ho lemalla. Tumellanong le khopolo ena ke lintho tse fumanoeng tse tsoang ho li-neurons tsa cippured cippured, moo ho ileng ha bontšoa hore secretion ea BDNF e etsa hore ho eketsoe mofuta oa protheine o thehiloeng holima mofuta o mong le o mong oa dendritic (Tanaka et al., 2008b). Bofokoli ba khopolo-taba ena ke hore ha ho na bopaki bo tobileng ba liteko tsa ntlafatso ea methapo ea kutlo ea li-neuron ka se le ntho e hlokahalang kapa e lekaneng bakeng sa likarabo tsa lithethefatsi tse lemalloang. Ebile, ho na le datha e bonts'ang kamano e rarahaneng ho feta lipakeng tsa liketsahalo tse peli: thibelo ea Cdk5 ho NAc e thibela bokhoni ba koae ho eketsa methapo ea methapo ho li-neuron tsa NAc, leha e le taba ea hore likarabo tse joalo tsa ts'ireletso ea cocaine le likarabelo tse khotsofatsang tsa koae (cocaine)Norrholm et al., 2003; Taylor le al., 2007). Ho hlakile hore ho na le mosebetsi o eketsehileng oa ho ithuta kamano e teng lipakeng tsa sebopeho sena sa boitšoaro.

Ntho e 'ngoe ea bohlokoa e ka re thusang ho feto-fetoha ke maikutlo ana ke hore liphetoho lipontšong tsa BDNF li ka hlahisa litholoana tse fapaneng haholo ho morphology le boitšoaro ho latela sebaka sa boko se hlahlojoang. Litlaleho tsa morao tjena li hlahisitse phapang e hlakileng pakeng tsa ts'ebetso ea BDNF ho hippocampus bapisoa le VTA (Berton et al., 2006; Eisch et al., 2003; Krishnan et al., 2007; Shirayama et al., 2002): Litlhaselo tsa BDNF ka hippocampus li tšoana le litlhare, athe infusions ea BDNF ho VTA kapa NAc e hlahisa litlamorao tse kang tsa protepressant. Mekhoa e ts'oanang e hlaha tšimong ea lithethefatsi. Haholo, BDNF e eketsehileng ho NAc e ntlafatsa boits'oaro bo khothalletsoang ke koae (cocaine)Graham et al., 2007; Horger et al., 1999), athe ho PFC BDNF e hatella boits'oaro bo tšoanang (Berglind et al., 2007). Ha ho makatse hore ho kenngoa ha BDNF ke koae ho boetse ho laoloa ka mokhoa o fapaneng libakeng tsena tse peli tsa boko, e leng mokhoa o tšehetsang phapang e fetang ea boitšoaro (Fumagalli et al., 2007).

Bopaki ba pele-pele bo ts'oaretse ho saena ha NF VerB ho taolo ea polasetine e kopantsoeng le boits'oaro. Leha ts'ebetso e tobileng eo liphetoho tsena li bang teng ka eona e sa tsejoe, mosebetsi o fetileng o bonts'itse hore p75NTR, e leng noka ea NF VerB, e fumaneha sebakeng sa pharalatso le hore p75NTR activation ke BDNF e hlokahala bakeng sa LTD. Le ha litšebelisano tsa BDNF-TrkB li ithutile ka mokhoa o pharaletseng ts'ebelisong ea lithethefatsi, datha tsena li fana ka maikutlo a tsela e 'ngoe ea ho feta ka NF VerB ea hore li tiisa lipatlisiso tse ling. Tumellanong le khopolo-taba ena, haufinyane re hlokometse hore tšebeliso ea bongata bo botle ba maikutlo a motho ea hanyetsang oa tsela ea NF VerB ho NAc e thibela bokhoni ba cocaine bo sa feleng ho eketsa letsoalo la methapo ea methapo ho liNC tsa MSC. Thibelo e joalo ea ho saena NF NFB e boetse e fifatsa tlhokomeliso ho litlamorao tse khahlisang tsa koae (coffine, Soc. Neurosci. Abstr. 611.5, 2007). Lintlha tsena, ho fapana le boemo ba Cdk5 e bontšitsoeng kaholimo, li tšehetsa khokahano lipakeng tsa ho eketseha ha dendritic arborization le boits'oaro ba boitšoaro ho cocaine, hape li totobatsa ho rarahana ha liketsahalo tsena le tlhoko ea thuto e eketsehileng.

Leha mosebetsi o fokolang o sebetsane le bohlokoa ba ho supa matšoao a ts'ebetso ea methapo ea methapo, ts'ebetsong ea rona laboratoring e senotse karolo bakeng sa BDNF le tsela e tlase ea IRS2-PI3K-Akt tseleng ea taolo ea boholo ba sele ea VTA dopaminergicRusso et al., 2007; Sklair-Tavron le al., 1996). Ka ho khetheha, tsamaiso e sa foleng ea opiate litonong e hlahisa boemo ba mamello le ts'ehetso ea 'mele linakong tsa pele tsa ho khaotsa tseo ho nahanoang hore li kenya letsoho ho eketseheng ha boitšoaro ba ho sebelisa lithethefatsi. Liteko tsa pejana li fumane hore infra-VTA e kenelletseng ea BDNF e thibela ho fokotseha ho bakoang ke morphine ho hlahisang boholo ba VTA ea neuron (Sklair-Tavron le al., 1996). Haufinyane tjena, re bonts'a hore nako ea ho mamella meputso, joalo ka ha e lekantsoe ke khetho ea sebaka, e ts'oana le tatellano ea nako ea lisele tse fokotsitsoeng tsa dopaminergic le hore liketsahalo tsena li kopantsoe ka mela ea li-signature tsa BDNF (Russo et al., 2007). Joalokaha ho boletsoe pejana, mekhoa ea biochemical signaling in VTA e tlase ho BDNF le receptor ea TrKB li laoloa ka mokhoa o fapaneng ke morphine e sa foleng: morphine activates PLCγ (Wolf le al., 2007; Wolf le al., 1999), e fokotsa ts'ebetso ea tsela ea IRS-PI3K-Akt (Russo et al., 2007; Wolf le al., 1999), hape e hlahisa litlamorao tse fapaneng ho ERK (bona kaholimo). Ka lebaka la bopaki ba morao-rao ba hore Akt o laola boholo ba mefuta e mengata ea lisele tsamaisong ea methapo ea kutlo (Backman et al., 2001; Kwon et al., 2006; Kwon et al., 2001; Scheidenhelm et al., 2005), re sebelisitse mekhoa ea phetisetso ea mofuta oa vaerale ho bontša ka kotloloho hore morphine e hlahisa mamello ea moputso ka thibelo ea tsela ea IRS2-PI3K-Akt le boholo bo fokolitsoeng ba VTA dopamine neurons. Litlamorao tsena ha lia ka tsa bonoa ka ho fetoloa hoa mola oa ERK kapa ho saena le PLCγ, hape ho supa bohlokoa ba IRS-PI3K-Akt ho tšoaea ketsahalo ena. Lithuto tsa nako e tlang li tla sebetsana le bohlokoa ba BDNF le IRS-PI3K-Akt litseleng tsa ho eketseha ha boipuso, paradigm e loketseng ho tsa bongaka ho lekola bokhoba ba tahi. Kutloisiso e kh of ol the o ea liphetoho tse nyolohang tsa li-neurotrophic factor kapa li-receptors tsa bona le liphofu tse tlase tsa Akt e tla sebetsana le mekhoa e ikhethang ea mamello ea moputso oa opiate mefuteng ea bokhoba. Ho feta moo, ho tla ba bohlokoa ho utloisisa karolo ea ho supa ha BDNF taolong ea ts'ebetso ea VTA ka har'a potoloho ea neural. Ntlheng ena, hoa thabisa ho hlokomela hore Pu et al. (2006) e bonts'itse hore ho khaola kamora ho pepesetsoa hoa koae khafetsa, maikutlo a thabisang ho li-dopamine neurons ho VTA a arabela ka mokhoa o matla ho susumetsoang ke ts'usumetso e fokolang ea presynaptic, sephetho se hlokang ho tšoaea hoa morao-rao BDNF-TrkB.

7. Karolo ea lintlha tse ling tsa neurotrophic ho polasetiki e hlahisitsoeng ke lithethefatsi le boits'oaro

Le ha puisano e kaholimo e bua ka BDNF le likarete tsa eona tse tšoaeang, ho na le bopaki ba hore lintlha tse ling tse 'maloa tsa methapo ea kutlo le litsela tsa bona tse tlase tsa tsela li boetse li susumetsa karabelo ea boitšoaro kapa ea biochemical ho lithethefatsi tsa tlhekefetso. NT3, joalo ka BDNF, e bontšitsoe ho khothaletsa likarabo tse khothatsang tsa koae ho boemo ba VTA (Pierce le Bari, 2001; Pierce et al., 1999). Tsamaiso e sa foleng ea morphine kapa cocaine up-e laola li-glial cell line-based neurotrophic factor (GDNF) ho supa ka har'a potoloho ea VTA-NAc, e ipheng ka ho khutlisa le ho hatella litlamorao tsa boits'oaro ba lithethefatsi tsena tsa tlhekefetso (Messer et al., 2000). Amphetamine e kenya motheo oa kholo ea li-fibroblast ukukhula (bFGF) ka har'a potoloho ea VTA-NAc le litoeba tsa bFGF li na le karabelo e sa utloahaleng mabapi le maikutlo a locomotor a susumetsoang ke ente ea amphetamine e phetoang (Flores et al., 2000; Flores le Stewart, 2000). Cytokine, ciliary neurotrophic factor (CNTF), e tsamaisoang ka kotloloho ho VTA, e ntlafatsa bokhoni ba koae ho kenyelletsa liphetoho tsa biochemical sebakeng sena sa boko; cocaine e eketsa li-cascades tse kenang kahare ho Janus kinase (JAK) le li-transducers tsa ponts'o le li-activator tsa transcript (STATs), e leng phello e neng e bakoa ke ts'oaetso e mpe ea CNTF (Behow et al., 1996a). Ho boetse ho na le bopaki ba hore maemo a sa foleng a morphine a feto-fetoha le maemo a kang a insulin - 1 (IGF1) ho VTA le libakeng tse ling tsa boko (Beitner-Johnson et al., 1992). Liphumano tsena tse ikhethileng li bonts'a hore mefuta e fapa-fapaneng ea methapo ea methapo ea kutlo e laola VTA-NAc sebetsa ho laola polasetiki ho lithethefatsi tsa tlhekefetso ka mekhoa e rarahaneng mme e totobatsa tlhoko ea lipatlisiso tse ngata tsa nako e tlang sebakeng sena.

8. Liphello

Lilemong tse leshome tse fetileng, re ekelitse kutloisiso ea rona ea kamoo lithethefatsi tsa tlhekefetso li laolang methapo ea methapo ea methapo le morphology ea lihlopha tse fapaneng tsa neuronal ho potoloha ha moputso oa boko. Tsoelo-pele ea morao-rao ho fetisetsoeng liphatsa tsa lefutso tsa vaerase e lumella mananeo a liprotheine tse tšoaeang lefu la nko e kenang ka nqane ho karolo e itseng ea kelello ea liphoofolo tse holileng ka botlalo ho ithuta likamano lipakeng tsa tlhekefetso ea lithethefatsi, morphology ea neuronal, le boits'oaro ba boits'oaro. Ka li-veal tsa viral tsa vaerase tse fumanehang habonolo, ho a khonahala ho hlahisa protheine e tsamaisang methapo ea methapo ea methapo le protheine ea fluorescent ho bona neuronal morphology (Clark et al., 2002). Ka hona, ka mekhoa e ntlafalitsoeng ea immunohistochemical ea ho ngola palo ea manonyeletso a itseng, ho a khonahala ho hlahloba liphetoho tse amanang le lithethefatsi le tse amanang le biochemical ho ho tšoaea hoa neurotrophic ka mokhoa o ikhethileng oa sele, ka hona e fana ka leseli la bohlokoa bakeng sa taolo ea ts'ebetso ea lithethefatsi ea boko bo tsoetseng pele. libaka tsa moputso. Ho sebelisa mekhoa e fapaneng ea boits'oaro ka mekhoa ea boitšoaro, ea 'mele, ea biochemical, le morphological, ho tla ba bonolo ho hlalosa mekhoa ea ts'ebetso ea ts'ebetso ka mokhoa o nepahetseng ho feta, ho kenyelletsa karolo e nepahetseng ea ts'ebetso ea neurotrophic ea ho bonts'a polasetiki e itšetlehileng ka boiphihlelo le ts'ebetso ea ho lemalla. Tsebo ena e ka lebisa nts'etsopele ea mehato e mengata ea bongaka e ka rarollang mathata a tlhaho a bakoang ke lithethefatsi tsa tlhekefetso libakeng tsa moputso oa boko mme ka hona a khutlisetsa ts'ebetso ea bokhoba ba batho.

Mongolo o botlaaseng ba leqephe

References