Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus.
Molecular and cellular characterization of nicotinic acetylcholine receptor subtypes in the arcuate nucleus of the mouse hypothalamus.
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DOI：
10.1111/ejn.13966
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发表时间：
2018-05-23
期刊：
影响因子：
--
通讯作者：
Picciotto MR
中科院分区：
文献类型：
--
作者：
Calarco CA;Li Z;Taylor SR;Lee S;Zhou W;Friedman JM;Mineur YS;Gotti C;Picciotto MR
尼古丁通过烟碱乙酰胆碱受体（nAChR）起作用，增加下丘脑弓状核（ARC）中的食欲原性刺豚鼠相关肽（AgRP）和食欲原性阿黑皮素（POMC）神经元的放电率，但尼古丁和其他nAChR激动剂减少小鼠的食物摄入量。病毒介导的ARC中所有神经元细胞类型中β4 nAChR亚基的敲低阻止了烟碱激动剂金雀花碱减少食物摄入，但尚不清楚β4亚基是否选择性地表达于致炎神经元中或其他nAChR亚型如何分布于该核中。使用翻译核糖体亲和纯化（TRAP）ARC组织从小鼠与核糖体标记在AgRP或POMC细胞，我们研究了nAChR亚基mRNA水平，使用实时PCR。AgRP和POMC细胞表达的nAChR亚基相当，α7 mRNA水平存在差异，α4水平存在差异趋势，但β4表达无差异。组装的nAChRs的免疫沉淀显示，β4亚基与α3、β2和α4形成组装通道，但在ARC中未发现其他亚基。最后，使用细胞类型选择性的、病毒递送的靶向β4或α7亚基的小发夹RNA，我们检查了AgRP或POMC细胞中每个亚基对尼古丁行为反应的贡献，完善了对这种摄食回路的尼古丁调节的理解。这些实验确定了一个更复杂的一套nAChRs表达ARC比其他下丘脑区域。因此，ARC似乎是尼古丁调节的一个特定靶点。下丘脑弓状核（ARC）内促排和促食神经元上的烟碱乙酰胆碱受体（nAChR）信号调节尼古丁对食物摄入的影响。nAChR亚基表达不受细胞类型的影响，β4亚基组装成nAChR，其组成与其他含β4的脑区不同，ARC中促排泌细胞和促食欲细胞中β4亚基的细胞类型选择性敲低可阻断尼古丁引起的摄食减少。
Nicotine, acting through nicotinic acetylcholine receptors (nAChRs), increases the firing rate of both orexigenic agouti-related peptide (AgRP) and anorexigenic pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC), yet nicotine and other nAChR agonists decrease food intake in mice. Viral-mediated knockdown of β4 nAChR subunit in all neuronal cell types in the ARC prevents the nicotinic agonist cytisine from decreasing food intake, but it is not known whether the β4 subunit is selectively expressed in anorexogenic neurons or how other nAChR subtypes are distributed in this nucleus. Using translating ribosome affinity purification (TRAP) on ARC tissue from mice with ribosomes tagged in either AgRP or POMC cells, we examined nAChR subunit mRNA levels using real-time PCR. Both AgRP and POMC cells express a comparable panel of nAChR subunits with differences in α7 mRNA levels and a trend for difference in α4 levels, but no differences in β4 expression. Immunoprecipitation of assembled nAChRs revealed that the β4 subunit forms assembled channels with α3, β2 and α4, but not other subunits found in the ARC. Finally, using cell type-selective, virally-delivered small hairpin RNAs targeting either the β4 or α7 subunit, we examined the contribution of each subunit in either AgRP or POMC cells to the behavioral response to nicotine, refining the understanding of nicotinic regulation of this feeding circuit. These experiments identify a more complex set of nAChRs expressed in ARC than in other hypothalamic regions. Thus, ARC appears to be a particular target of nicotinic modulation. Nicotinic acetylcholine receptor (nAChR) signaling on both anorexogenic and orexogenic neurons in the arcuate nucleus of the hypothalamus (ARC) regulates the effects of nicotine on food intake. nAChR subunit expression, is not segregated by cell type, the β4 subunit assembles into nAChRs with a different composition than in other β4 containing brain regions, and cell type selective knockdown of the β4 subunit in either anorexogenic and orexogenic cells in the ARC blocks the reduction in feeding due to nicotine.
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影响因子：
7.7
作者：
Henry FE;Sugino K;Tozer A;Branco T;Sternson SM
通讯作者：
Sternson SM
DOI：
10.1016/0169-328x(92)90244-6
发表时间：
1992-12-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
DINELEYMILLER, K;PATRICK, J
通讯作者：
PATRICK, J
陷阱seq定义了下丘脑和脑干LEPB神经元的新型标记。
影响因子：
8.1
作者：
Allison MB;Patterson CM;Krashes MJ;Lowell BB;Myers MG Jr;Olson DP
通讯作者：
Olson DP
影响因子：
3.6
作者：
Gotti, Cecilia;Moretti, Milena;Marks, Michael J.
通讯作者：
Marks, Michael J.
哺乳动物烟碱乙酰胆碱受体：从结构到功能。
影响因子：
33.6
作者：
Albuquerque EX;Pereira EF;Alkondon M;Rogers SW
通讯作者：
Rogers SW