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Science֪ʳأ㲻һС˽ս

ʱ䣺2018-07-11 ȶȣ

ԹԣʳΪ족ɴ˿ɼԡҪԡ

ΪdzԵ徲սҷع͡ƤЬҡжʳÿ´ѽڣ򵼸ԳгʼۣǵĻȨԡնŵĪҲ̹ԣдij־Ϊӡ

ڡԡ񾭻ƣоעԹ״ǡСĽAgRPԪTHԪPOMCԪʳΪ[1, 2]ǣԡֻһ

Թ״˵ؽʳΪ

һССнںˣTuberal nucleus, TNѧͲ鶯жоද̽оٻᵼʳ֢ں˹ЧҲշݹᾶʣעں˿ʳΪء

ʻߣͼң

20180706գScience־¼оԺYu FuڵҪ[3]ǷںأSomatostatin, SSTԪڽʳΪҪãЩԪͶ䵽ԺˣPVNƴˣBNSTԵؽʳƪ״ηںڼ·еĹЧһչʳ񾭻ơ

Yu Fu


Ч

1.óͷС󼤻TNSSTԪ

УںˣTNԣLHͷˣTMNԴڱSSTΪǣСжԽںSSTԪTNSSTоǽSST-CreСAi14ӽӴSSTԪɫӫѰףˣǿɿSSTԪеܡ

߷SSTԪڹ״ˣArcTNдڱ棨ͼ1A黯ЧעArcSSTԪAgRPTHPOMCԪ٣ͼ1BTNΧSSTԪLHMCHLHOrxTMNHDCԪ޹꣨ͼ1CЩԪʳΪл[4, 5]

ס޽ʳøǻע伢شóͷС󣬣TNSSTԪc-fosˮƽߡĤƬǯʵУ뼢غTNSSTԪͷƵעTNSSTԪ

ͼ1 óͷС󼤻TNSSTԪ

2.TNSSTԪؽʳΪ

ʶTNSSTԪ״̬֮󣬣ΪоTNSSTԪڽʳΪеijҪԣSST-CreСTNעAAV-DIO-hM3DAAV-DIO-KORDҩDTNSSTԪշСʳΪڽʳʳһʱ䡢ÿοҧʳʱͽʳƵҩTNSSTԪСʳΪ̭߻ͨŴѧҪ켤TNSSTԪۣͬͼ2A-N

ΪоTNSSTԪЧĺЧӦSST-CreСTNעAAV-flex-taCasp3յTNSSTԪ10ܺ󣬣Сͼ2O

оע佱շʳΪΪ̽TNSSTԪϲЧӦʹλƫãCPPΪѧʽҩDTNSSTԪշСƫΪͼ2P

ͼ2 TNSSTԪؽʳΪ

3.TNSSTԪͨPVNBNSTʳΪ

ʶTNSSTԪڽʳΪеijҪ֮󣬣߾̽SST-CreСTNעAAV-FLEX-GFPʾЩԪҪΪPVNBNSTCeAPAGPVTPBNͳһȺԪͶ䵽2ArcAgRPġһһͶ䷽[6]ͼ3A-E

Ϊ̽·ؽʳΪSST-CreСTNעAAV-DIO-ChR2PVNBNSTCeAPAGֲˣ⼤TNSST-PVNTNSST-BNST·շʳΪ⼤·Ӱ죨ͼ3F-I

ͼ3 TNSSTԪͨPVNBNSTʳΪ

4.TNSSTԪҪΪGABAԪ

ʶTNSSTԪЧ󣬣߾Լϸоͨԭλӽ黯ʵ飬ǷTNSSTԪҪΪ-ᣨGABAԪȰԪ޽ͼ4A-D

ΪоTNSSTԪεЧӦʳΪSST-CreСTNעAAV-DIO-hM3DPVNעCNOGABAA׿ɰĵǷѧTNSST-PVN·շʳΪͬʱGABAʹշЧӦͼ4EArcAgRPԪػ[7]עTNSSTԪͨͶʳΪ

ͼ4 TNSSTԪҪΪGABAԪ


ܽ


ʳΪ죬ԡĵĹЧоעArcAgRPԪΪ·Ľ㡣ϵѧŴѧŴѧΪѧҪ죬״η·һ㡪TNSSTԪTNSSTԪշʳΪƻɱTNSSTԪ̭ʳΪӶصģTNSSTԪҪͨPVNBNSTؽʳΪչ˽ʳΪ񾭻ƣڼʳ֪ǸʶԼΪʲô롰ԡ

UG һֱע񾭡лشоϣΪоṩ¹ߺоƻٴתͻƣ




οס


1.Gropp, E., et al., Agouti-related peptide-expressing neurons are mandatory for feeding. Nat Neurosci, 2005. 8(10): p. 1289-91.
2.Zhang, X. and A.N. van den Pol, Hypothalamic arcuate nucleus tyrosine hydroxylase neurons play orexigenic role in energy homeostasis. Nat Neurosci, 2016. 19(10): p. 1341-7.
3.Luo, S.X., et al., Regulation of feeding by somatostatin neurons in the tuberal nucleus. Science, 2018.361(6397): p. 76-81.
4.Whiddon, B.B. and R.D. Palmiter, Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling. J Neurosci, 2013. 33(5): p. 2009-16.
5.Haas, H. and P. Panula, The role of histamine and the tuberomamillary nucleus in the nervous system. Nat Rev Neurosci, 2003. 4(2): p. 121-30.
6.Betley, J.N., et al., Parallel, redundant circuit organization for homeostatic control of feeding behavior. Cell, 2013. 155(6): p. 1337-50.
7.Garfield, A.S., et al., A neural basis for melanocortin-4 receptor-regulated appetite. Nat Neurosci, 2015. 18(6): p. 863-71.

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