Menyhért Judit, Wittmann Gábor, Lechan Ronald M, Keller Eva, Liposits Zsolt, Fekete Csaba
Department of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, 43 Szigony Street, 1083 Budapest, Hungary.
Endocrinology. 2007 Sep;148(9):4276-81. doi: 10.1210/en.2007-0390. Epub 2007 May 24.
Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered anorexigenic peptide. In rodents, CART inhibits food intake and is expressed in the anorexigenic alpha-MSH- but not in the orexigenic neuropeptide Y (NPY)- and agouti-related protein (AGRP)-synthesizing neurons of the arcuate nucleus. To understand whether CART is similarly expressed in feeding-related neuronal groups of the human hypothalamus as observed in rodents, colocalization of CART with alpha-MSH, NPY, AGRP, and melanin-concentrating hormone was studied using double-labeling immunofluorescence and confocal microscopy on human hypothalamic tissues obtained at autopsy. Unlike in rodents, we observed that CART is absent from the perikarya and axons of alpha-MSH-synthesizing neurons, but expressed in approximately one third of NPY/AGRP neurons in the human infundibular nucleus. In the lateral hypothalamus of the humans, colocalization of CART and melanin-concentrating hormone was observed, similar to that described in rodents. The anatomy of CART-containing neurons in the human infundibular nucleus differs markedly from that observed in the rodent brain, raising the question whether the colocalization of CART with orexigenic NPY and AGRP neurons is associated with an orexigenic role of CART in the human brain.
可卡因和苯丙胺调节转录肽(CART)是一种最近发现的厌食肽。在啮齿动物中,CART抑制食物摄入,并在弓状核中厌食性的α-促黑素细胞激素(α-MSH)合成神经元中表达,但不在促食欲的神经肽Y(NPY)和刺鼠相关蛋白(AGRP)合成神经元中表达。为了了解CART在人类下丘脑与进食相关的神经元群中是否与在啮齿动物中观察到的情况类似地表达,我们使用双标记免疫荧光和共聚焦显微镜对尸检获得的人类下丘脑组织进行研究,观察CART与α-MSH、NPY、AGRP和促黑素细胞激素的共定位情况。与啮齿动物不同,我们观察到α-MSH合成神经元的胞体和轴突中不存在CART,但在人类漏斗核中约三分之一的NPY/AGRP神经元中表达。在人类下丘脑外侧,观察到CART与促黑素细胞激素的共定位,这与在啮齿动物中描述的情况类似。人类漏斗核中含CART神经元的解剖结构与在啮齿动物脑中观察到的明显不同,这就提出了一个问题,即CART与促食欲的NPY和AGRP神经元的共定位是否与CART在人类大脑中的促食欲作用有关。