近日,，據(jù)美國(guó)物理學(xué)家組織網(wǎng)報(bào)道,，美國(guó)耶魯大學(xué)科學(xué)家發(fā)現(xiàn)了一種關(guān)鍵細(xì)胞機(jī)理，能幫大腦控制我們每天的食物攝入量,、體重以及干活時(shí)能不能精力充沛,。相關(guān)論文發(fā)表在《神經(jīng)科學(xué)雜志》(The Journal of Neuroscience)上。
下丘腦部位的神經(jīng)元調(diào)節(jié)著體溫,、攝食等基本機(jī)能,，維持著身體的能量平衡，它們發(fā)出的軸突遍布于整個(gè)神經(jīng)系統(tǒng),。這里有兩種功能相反的神經(jīng)元,，一種是黑色素濃集激素（MCH）神經(jīng)元，另一種是促甲狀腺激素釋放激素（TRH）神經(jīng)元,?？茖W(xué)家和制藥公司一直在追蹤MCH神經(jīng)元在控制攝食和能量水平中的作用，此前的研究顯示，MCH神經(jīng)元聯(lián)系著高熱量攝入與低能量輸出,，使實(shí)驗(yàn)室動(dòng)物吃得更多,、睡得更多卻沒(méi)有精力。
耶魯大學(xué)研究人員發(fā)現(xiàn)了另一種反效果的神經(jīng)元,，以促甲狀腺激素釋放激素TRH為神經(jīng)遞質(zhì),，會(huì)減少食物攝入，減輕體重,，增加身體活動(dòng)量。根據(jù)他們對(duì)小鼠大腦的研究顯示,，這兩個(gè)系統(tǒng)的作用截然相反,，共同協(xié)助保持動(dòng)物基本機(jī)能的平衡,。盡管TRH是一種有興奮性的神經(jīng)遞質(zhì)，它們卻以引入更多抑制突觸的方式抑制MCH細(xì)胞,，但TRH對(duì)其他類(lèi)神經(jīng)元卻沒(méi)什么影響，即使這些神經(jīng)元也和能量調(diào)控有關(guān),。
論文高級(jí)作者,、耶魯大學(xué)醫(yī)學(xué)院神經(jīng)外科教授安東尼·波爾說(shuō)：“這兩種神經(jīng)元在突觸的水平相互作用，為我們研究大腦怎樣控制攝入的食物量,、睡眠時(shí)間等提供了線索,。（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
