Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam Amsterdam, Netherlands.
Department of Neuropsychiatric Disorders, Netherlands Institute for Neuroscience, An Institute of the Royal Netherlands Academy of Arts and Sciences Amsterdam, Netherlands.
Front Neurosci. 2014 May 15;8:106. doi: 10.3389/fnins.2014.00106. eCollection 2014.
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.
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.
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.
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 α-melanocyte stimulating hormone.
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.
很长一段时间以来,人们就知道血清素在调节摄食行为和能量代谢方面发挥着作用。血清素转运体(SERT)通过调节突触间隙中血清素的可用性,在血清素信号传递中起着至关重要的作用。人类中与血清素能信号传递相关的神经解剖结构在很大程度上尚不清楚,到目前为止,还没有研究过 SERT 免疫反应与体重的关系。
阐明 SERT 免疫反应在人类下丘脑的分布,并比较瘦人和超重人群下丘脑中漏斗核(IFN)的 SERT 免疫反应。
首先,我们通过免疫组织化学方法研究了六个死后下丘脑的 SERT 沿头尾轴的分布。其次,我们估计了瘦人和超重人群 IFN 中的 SERT 免疫反应。最后,对 SERT 与神经肽 Y(NPY)和黑素细胞群进行双重标记,以进一步确定显示篮状 SERT 染色的细胞。
SERT 免疫反应在整个下丘脑的纤维中广泛表达,在 IFN 中最强。IFN 中的免疫反应在超重者中较低(p = 0.036)。IFN 中的篮状染色强烈提示存在突触支配。极少数细胞显示 SERT 与 NPY、肥胖相关蛋白和α-黑素细胞刺激素的双重标记。
SERT 在人类下丘脑广泛表达。在 IFN 中观察到强烈的 SERT 免疫反应,这是一个对食欲调节很重要的区域,结合超重和肥胖人群 IFN 中 SERT 免疫反应较低,可能表明下丘脑 SERT 在人类肥胖中起作用。