Decreased serotonin transporter immunoreactivity in the human hypothalamic infundibular nucleus of overweight subjects
Decreased serotonin transporter immunoreactivity in the human hypothalamic infundibular nucleus of overweight subjects
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DOI：
10.3389/fnins.2014.00106
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发表时间：
2014-05-15
影响因子：
4.3
通讯作者：
Alkemade, Anneke
中科院分区：
文献类型：
--
作者：
Borgers, Anke J.;Koopman, Karin E.;Alkemade, Anneke
背景：血清素在摄食行为和能量代谢的调节中起着重要作用，这一事实早已为人所知。血清素转运体（SERT）通过调节突触间隙中血清素的可用性，在血清素信号传导中起着至关重要的作用。人类血清素能信号的神经解剖学基础在很大程度上是未知的，直到现在，SERT免疫反应性与体重的关系还没有被调查。目的：阐明SERT免疫反应性在整个人类下丘脑的分布，并比较在瘦和超重受试者中，SERT免疫反应性在小脑核（相当于弓形核）中的分布。设计：首先，我们用免疫组织化学的方法研究了6只死后下丘脑的背尾轴上血清素转运体（SERT）的分布。其次，我们估计了瘦和超重受试者IFN中的SERT免疫反应性。最后，用神经肽Y （NPY）和黑素皮质素细胞群对SERT进行双重标记，以进一步鉴定显示篮状SERT染色的细胞。结果：sert免疫反应性在整个下丘脑的纤维中普遍表达，并在IFN中最强。超重受试者IFN的免疫反应性较低（p = 0.036）。IFN的篮状染色高度提示突触神经支配。极少数细胞显示NPY、agouti相关蛋白和α -黑素细胞刺激激素的SERT双标记。结论：SERT在人类下丘脑中普遍表达。在IFN（食欲调节的重要区域）中观察到强烈的SERT免疫反应性，与超重和肥胖受试者的IFN中较低的SERT免疫反应性相结合，可能指出下丘脑SERT在人类肥胖中的作用。
Context: That serotonin plays a role in the regulation of feeding behavior and energy metabolism has been known for a long time. Serotonin transporters (SERT) play a crucial role in serotonin signaling by regulating its availability in the synaptic cleft. The neuroanatomy underlying serotonergic signaling in humans is largely unknown, and until now, SERT immunoreactivity in relation to body weight has not been investigated.Objective: To clarify the distribution of SERT immunoreactivity throughout the human hypothalamus and to compare SERT immunoreactivity in the infundibular nucleus (IFN), the human equivalent of the arcuate nucleus, in lean and overweight subjects.Design: First, we investigated the distribution of serotonin transporters (SERT) over the rostro-caudal axis of six post-mortem hypothalami by means of immunohistochemistry. Second, we estimated SERT immunoreactivity in the IFN of lean and overweight subjects. Lastly, double-labeling of SERT with Neuropeptide Y (NPY) and melanocortin cell populations was performed to further identify cells showing basket-like SERT staining.Results: SERT-immunoreactivity was ubiquitously expressed in fibers throughout the hypothalamus and was the strongest in the IFN. Immunoreactivity in the IFN was lower in overweight subjects (p = 0.036). Basket-like staining in the IFN was highly suggestive of synaptic innervation. A very small minority of cells showed SERT double labeling with NPY, agouti-related protein and alpha-melanocyte stimulating hormone.Conclusions: SERT is ubiquitously expressed in the human hypothalamus. Strong SERT immunoreactivity, was observed in the IFN a region important for appetite regulation, in combination with lower SERT immunoreactivity in the IFN of overweight and obese subjects, may point toward a role for hypothalamic SERT in human obesity.