Sebopeho sa Sehlopha sa Sehlopha sa Epigenetic ho Fosb Gene Controls Ho itšetleha ka khatello ea kelello ea sechaba (2017)

Neuropsychopharmacology. 2017 May 2. Doi: 10.1038 / npp.2017.88.

Hamilton PJ1, Burek DJ1, Lombroso SI2, RL Rate3, Robison AJ4, Nestler EJ1, Heller EA2.

inahaneloang

Matšoenyeho a sa feleng a taolo ea sechaba a laola polelo ea Fosb ho bokellane ba nyutlelie (NAc) ho khothaletsa ho bokella mofuta o khethehileng oa ΔFosB likarolong tse peli tse mahareng tsa "spiny neuron" (MSN) sebakeng sena. ΔFosB e hlohlelletsoa ka mokhoa o khethiloeng ho li-D1-MSNs ho NAc ea litoeba tse ikemiselitseng, le ho D2-MSNs ea litoeba tse kotsing. Leha ho le joalo, ha ho tsejoehale ka litlamorao tsa ho kenella ho joalo ho khethiloeng, haholo-holo ho D2-MSNs. Phuputso ena e ile ea hlahloba hore na mofuta oa sele o itseng oa taolo ea mofuta oa Fosb ho NAc o laola joang monyetla oa khatello ea taolo ea khatello ea sechaba. Liphetoho tsa nalane ea morao-rao ea phetolelo (HPTMs) li ne li lebisitsoe ho Fosb ka ho sebelisa liprotheine tse entsoeng ka enjene ea Zenzu (ZFPs). Fosb-ZFPs e ile ea qobelloa ho khatiso e hatisang, G9a, e khothalletsang histone methylation kapa activ actival, p65 e khothalletsang histone acetylation. Li-ZFP tsena li ile tsa hlahisoa ho D1- vs D2-MSN li sebelisa polelo e buang ka vaerase e itšetlehileng ka NAc ea litoeba tse fetotsoeng bakeng sa Cre-recombinase ho li-subtypes tsena tsa MSN. Re fumana hore khatello ea khatello ea maikutlo e laoloa ka mokhoa o hlakileng ke mofuta o itseng oa sele le HPTM e lebisitsoeng. Re tlaleha hore Fosb e lebisitsoeng histone acetylation ho D2-MSNs kapa histone methylation ho D1-MSNs e khothaletsa khatello ea maikutlo, e ts'oenyehileng joalo ka phenotype, ha histone methylation ho D2-MSNs kapa histone acetylation ho D1-MSNs e eketsa ho tsitsinyeha hoa khatello ea sechaba e hlalosoa ka boitsoaro ba tšebelisano ea sechaba le likhetho tsa sucrose. Mosebetsi ona o hlahisa ponts'o ea pele ea ho hlaseloa ha cellone le gene ka kotloloho ho li-modone tse etsahalang ka tlhaho tse laolang liketsahalo tsa khatello ea maikutlo. Mokhoa ona oa ho hlophisa liphetoho o amanang le 'mele, o fetolang liphetoho tsa' mele polelong ea liphatsa tsa lefutso, o senola liphapang tse hlakileng taolong ea tlholeho e entsoeng ke Fosb gene manipulation ho li-subtypes tsa MSN.

PMID: 28462942

DOI: 10.1038 / npp.2017.88