Broberger C, De Lecea L, Sutcliffe J G, Hökfelt T
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
J Comp Neurol. 1998 Dec 28;402(4):460-74.
Cells in the lateral hypothalamus and in the arcuate nucleus play prominent roles in the central control of food intake; however, a neurochemical link connecting these potential components of a hypothalamic circuitry regulating energy metabolism remains to be established. In the present study, the topographical relationship between cells expressing mRNAs encoding melanin-concentrating hormone and the newly discovered neuropeptide family hypocretins/orexins was studied in the rat and mouse lateral hypothalamus by using double-labeling in situ hybridization. Cells expressing the two mRNAs formed completely distinct populations, with hypocretin/orexin cells located primarily perifornically and in the magnocellular lateral hypothalamic nucleus; melanin-concentrating hormone cells extended in a wider area both laterally and periventricularly and appeared to partly surround the hypocretin/orexin population. In the arcuate nucleus, cells expressing neuropeptide Y and agouti gene-related protein were studied by routine fluorescence and/or confocal microscopy immunohistochemistry. Double staining demonstrated that a large proportion of the neuropeptide Y-positive cell bodies in this nucleus also contained agouti gene-related protein-like immunoreactivity. Moreover, these two peptides also coexisted in nerve terminals surrounding and in close relationship to perikarya and processes of both hypocretin/orexin- and melanin-concentrating hormone-immunoreactive cells in the lateral hypothalamus, whereby the former appeared to receive a more dense innervation. These results thus provide evidence for an arcuate-lateral hypothalamic neuropeptide Y/agouti gene-related protein pathway. Furthermore, the results implicate hypocretin/orexin and melanin-concentrating hormone-expressing cells as downstream targets in neuropeptide Y-induced feeding.
下丘脑外侧区和弓状核的细胞在食物摄入的中枢控制中发挥着重要作用；然而，连接下丘脑调节能量代谢回路中这些潜在组成部分的神经化学联系仍有待建立。在本研究中，通过使用双标记原位杂交技术，在大鼠和小鼠下丘脑外侧区研究了表达编码黑色素聚集激素的mRNA的细胞与新发现的神经肽家族促食欲素/食欲素之间的拓扑关系。表达这两种mRNA的细胞形成了完全不同的群体，促食欲素/食欲素细胞主要位于穹窿周和下丘脑外侧大细胞核中；黑色素聚集激素细胞在外侧和脑室周围的更广泛区域延伸，似乎部分包围了促食欲素/食欲素细胞群体。在弓状核中，通过常规荧光和/或共聚焦显微镜免疫组织化学研究了表达神经肽Y和刺鼠基因相关蛋白的细胞。双重染色表明，该核中大部分神经肽Y阳性细胞体也含有刺鼠基因相关蛋白样免疫反应性。此外，这两种肽也共存于下丘脑外侧区促食欲素/食欲素和黑色素聚集激素免疫反应性细胞的胞体和突起周围及密切相关的神经末梢中，其中前者似乎接受更密集的神经支配。因此，这些结果为弓状核-下丘脑外侧区神经肽Y/刺鼠基因相关蛋白通路提供了证据。此外，这些结果表明促食欲素/食欲素和表达黑色素聚集激素的细胞是神经肽Y诱导进食的下游靶点。
