Methyleugenol counteracts anorexigenic signals in association with GABAergic inhibition in the central amygdala
Methyleugenol counteracts anorexigenic signals in association with GABAergic inhibition in the central amygdala
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甲基丁香酚抵消与中央杏仁核 GABA 能抑制相关的厌食信号
DOI：
10.1016/j.neuropharm.2018.08.034
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发表时间：
2018-10
影响因子：
4.7
通讯作者：
Li Fei
中科院分区：
文献类型：
--
作者：
Zhu Tailin;Yan Yuhua;Deng Shining;Liu Yan Mei;Fan Hui Ran;Ma Bingke;Meng Bo;Mei Bing;Li Wei Guang;Li Fei
饱食感、疾病或食物不好吃都可能抑制进食。杏仁核中央核（CeA）被认为是处理多个促凋亡信号的关键区域，但详细的细胞和分子机制仍不清楚。我们发现，甲基丁香酚（ME），一种新型的A型离子型γ-氨基丁酸受体（GABAARs）激动剂，可显著抵消与CeA中GABA能抑制相关的饱腹感或疾病引起的促食欲作用。在电生理上，ME增强了CeA的GABA能传递，抑制了CeA神经元的兴奋性。在行为上，ME增加了未处理小鼠的摄食，但不影响自发活动和基础焦虑。值得注意的是，全身和CeA特异性递送ME显着拯救饱腹感或疾病诱导的摄食抑制。ME的作用主要依赖于CeA的GABAARs。事实上，病毒介导的GABAAR γ2亚基的CeA区域特异性基因敲低在很大程度上消除了上述药理学作用，而其在CeA中产生蛋白激酶C-δ（PKC-δ）的GABA能神经元亚群中的重新表达恢复了ME对促凋亡信号的作用。综上所述，这些结果揭示了一种新的分子机制，反厌食信号依赖于GABA能抑制CeA，这表明ME作为治疗厌食症的主要化合物的可能性。
Feeding can be inhibited by satiety, sickness, or food unpalatability. The central nucleus of the amygdala (CeA) has been considered the key region for processing multiple anorexigenic signals, although the detailed cellular and molecular mechanisms remain largely unclear. Here we identify that methyleugenol (ME), a novel agonist of A type ionotropic γ-aminobutyric acid receptors (GABAARs), significantly counteracts the anorexigenic effects caused by satiety or sickness in association with GABAergic inhibition in the CeA. Electrophysiologically, ME enhanced GABAergic transmission and repressed neuronal excitability of the CeA. Behaviorally, ME increased feeding but not affect locomotor activity and basal anxiety in naïve mice. Notably, both systemic and CeA-specific delivery of ME significantly rescued satiety- or sickness-induced inhibition of feeding. The effects of ME were mainly dependent on the GABAARs in the CeA. Indeed, viral-mediated, the CeA region-specific genetic knockdown of the γ2 subunit of GABAARs largely abolished the above pharmacological effects, while its re-expression in a subpopulation of GABAergic neurons in the CeA, that produce protein kinase C-δ (PKC-δ), recovered the effects of ME on anorexigenic signals. Taken together, these results reveal a novel molecular mechanism for counter-anorexigenic signals dependent on GABAergic inhibition in the CeA, suggesting the possibility of ME as a leading compound for anorexia treatment.
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影响因子：
5
作者：
Yano, Shingo;Suzuki, Yasuyuki;Miyamoto, Ken-ichi
通讯作者：
Miyamoto, Ken-ichi
影响因子：
64.8
作者：
Tye, Kay M.;Prakash, Rohit;Kim, Sung-Yon;Fenno, Lief E.;Grosenick, Logan;Zarabi, Hosniya;Thompson, Kimberly R.;Gradinaru, Viviana;Ramakrishnan, Charu;Deisseroth, Karl
通讯作者：
Deisseroth, Karl
影响因子：
64.8
作者：
Wu, Qi;Clark, Michael S.;Palmiter, Richard D.
通讯作者：
Palmiter, Richard D.
GABA 转运蛋白 1 缺乏导致精神分裂症样行为表型
影响因子：
3.7
作者：
Yu Z;Fang Q;Xiao X;Wang YZ;Cai YQ;Cao H;Hu G;Chen Z;Fei J;Gong N;Xu TL
通讯作者：
Xu TL
DOI：
10.1007/bf03403643
发表时间：
2004-05-01
影响因子：
4.3
作者：
Johnston, E;Johnson, S;Johnston, M
通讯作者：
Johnston, M