J. Neurosci.：美揭示控制体重和能量的细胞机理

近日，据美国物理学家组织网报道，美国耶鲁大学科学家发现了一种关键细胞机理，能帮大脑控制我们每天的食物摄入量、体重以及干活时能不能精力充沛。相关论文发表在《神经科学杂志》(The Journal of Neuroscience)上。

下丘脑部位的神经元调节着体温、摄食等基本机能，维持着身体的能量平衡，它们发出的轴突遍布于整个神经系统。这里有两种功能相反的神经元，一种是黑色素浓集激素（MCH）神经元，另一种是促甲状腺激素释放激素（TRH）神经元。科学家和制药公司一直在追踪MCH神经元在控制摄食和能量水平中的作用，此前的研究显示，MCH神经元联系着高热量摄入与低能量输出，使实验室动物吃得更多、睡得更多却没有精力。

耶鲁大学研究人员发现了另一种反效果的神经元，以促甲状腺激素释放激素TRH为神经递质，会减少食物摄入，减轻体重，增加身体活动量。根据他们对小鼠大脑的研究显示，这两个系统的作用截然相反，共同协助保持动物基本机能的平衡。尽管TRH是一种有兴奋性的神经递质，它们却以引入更多抑制突触的方式抑制MCH细胞，但TRH对其他类神经元却没什么影响，即使这些神经元也和能量调控有关。

论文高级作者、耶鲁大学医学院神经外科教授安东尼·波尔说：“这两种神经元在突触的水平相互作用，为我们研究大脑怎样控制摄入的食物量、睡眠时间等提供了线索。（生物谷Bioon.com）

doi:10.1523/?JNEUROSCI.5966-11.2012
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Thyrotropin-Releasing Hormone (TRH) Inhibits Melanin-Concentrating Hormone Neurons: Implications for TRH-Mediated Anorexic and Arousal Actions

Xiaobing Zhang and Anthony N. van den Pol

Thyrotropin-releasing hormone (TRH) increases activity and decreases food intake, body weight, and sleep, in part through hypothalamic actions. The mechanism of this action is unknown. Melanin-concentrating hormone (MCH) and hypocretin/orexin neurons in the lateral hypothalamus (LH) together with neuropeptide Y (NPY) and proopiomelanocortin (POMC) neurons in the arcuate nucleus play central roles in energy homeostasis. Here, we provide electrophysiological evidence from GFP-reporter transgenic mouse brain slices that shows TRH modulates the activity of MCH neurons. Using whole-cell current-clamp recording, we unexpectedly found that TRH and its agonist, montrelin, dose-dependently inhibited MCH neurons. Consistent with previous reports, TRH excited hypocretin/orexin neurons. No effect was observed on arcuate nucleus POMC or NPY neurons. The TRH inhibition of MCH neurons was eliminated by bicuculline and tetrodotoxin, suggesting that the effect was mediated indirectly through synaptic mechanisms. TRH increased spontaneous IPSC frequency without affecting amplitude and had no effect on miniature IPSCs or EPSCs. Immunocytochemistry revealed little interaction between TRH axons and MCH neurons, but showed TRH axons terminating on or near GABA neurons. TRH inhibition of MCH neurons was attenuated by Na+-Ca2+ exchanger (NCX) inhibitors, TRPC channel blockers and the phospholipase C inhibitor U-73122. TRH excited LH GABA neurons, and this was also reduced by NCX inhibitors. Finally, TRH attenuated the excitation of MCH neurons by hypocretin. Together, our data suggest that TRH inhibits MCH neurons by increasing synaptic inhibition from local GABA neurons. Inhibition of MCH neurons may contribute to the TRH-mediated reduction in food intake and sleep.