Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
Leptin activates distinct projections from the dorsomedial and ventromedial hypothalamic nuclei
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DOI：
10.1073/pnas.95.2.741
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发表时间：
1998-01-20
影响因子：
11.1
通讯作者：
Saper, CB
中科院分区：
文献类型：
--
作者：
Elmquist, JK;Ahima, RS;Saper, CB
瘦素对进食、新陈代谢和神经内分泌状态具有深远的影响，有证据表明下丘脑协调这些反应，尽管瘦素参与的特定大脑通路仍然不清楚，下丘脑室旁核（PVH）调节垂体功能和进食，并支配自主神经节前神经元，使其成为调节瘦素的许多反应的候选者，室旁区，下丘脑前部区域，接受来自瘦素的密集神经支配。视交叉上核，被认为整合了昼夜节律和代谢信息，我们研究了瘦素给药激活的大鼠大脑中神经元的分布，通过将 Fos 免疫组织化学与霍乱毒素-b 的逆行转运结合起来，这些神经元也投射到 PVH 或室旁区，静脉注射瘦素特征性地激活了几个细胞组，包括下丘脑腹内侧核、下丘脑背内侧核 (DMH) 和 PVH，当示踪剂注射集中在室旁区时，在下丘脑腹内侧核的背内侧分区中观察到许多双标记细胞。该预测可能为整合代谢和昼夜节律信息以调节下丘脑-垂体轴提供解剖学基础。当霍乱毒素-b 注射集中在 PVH 中时，在尾部 DMH 内发现了许多双标记细胞。因此，PVH 的特定神经内分泌和自主元件的激活可能是由 DMH 中产生的瘦素激活的传入信号触发的。我们的结果表明，一组离散的下丘脑通路可能是瘦素的自主、内分泌和行为影响的基础。
Leptin has profound effects on feeding, metabolism, and neuroendocrine status, Evidence indicates that the hypothalamus coordinates these responses, though the specific brain pathways engaged by leptin remain obscure, The paraventricular nucleus of the hypothalamus (PVH) regulates pituitary gland function and feeding, and innervates autonomic preganglionic neurons, making it a candidate to regulate many of the responses to leptin, The subparaventricular zone, an anterior hypothalamic region receiving dense innervation from the suprachiasmatic nucleus, is thought to integrate circadian and metabolic information, We investigated the distribution of neurons in the rat brain activated by leptin administration that also project to the PVH or the subparaventricular zone by coupling immunohistochemistry for Fos with retrograde transport of cholera toxin-b, Intravenous leptin characteristically activated several cell groups including the ventromedial hypothalamic nucleus, the dorsomedial hypothalamic nucleus (DMH), and the PVH, When tracer injections were centered in the subparaventricular zone, many double-labeled cells were observed in the dorsomedial subdivision of the ventromedial hypothalamic nucleus. This projection may provide an anatomic substrate for integration of metabolic and circadian information to regulate the hypothalamo-pituitary axis, When cholera toxin-b injections were centered in the PVH, many double-labeled cells were found within the caudal DMH. Hence, activation of specific neuroendocrine and autonomic elements of the PVH may be triggered by leptin-activated afferents arising in the DMH. Our results demonstrate that a discrete set of hypothalamic pathways may underlie leptin's autonomic, endocrine, and behavioral effects.