Lee Eun Y, Hwang Young G, Lee Hyun S
Department of Anatomy, School of Medicine, Konkuk University, 05029 Seoul, Republic of Korea.
Department of Anatomy, School of Medicine, Konkuk University, 05029 Seoul, Republic of Korea; Research Institute of Medical Science, School of Medicine, Konkuk University, 05029 Seoul, Republic of Korea.
Brain Res. 2017 Feb 15;1657:16-28. doi: 10.1016/j.brainres.2016.11.025. Epub 2016 Dec 5.
Based on the importance of tuberomammillary nucleus (TMN) as a target for feeding/arousal-related functions, we aimed in the present study to investigate hypothalamic neuronal origin of neuropeptide Y (NPY) and cocaine- and amphetamine-regulated transcript (CART) fibers projecting to the histaminergic nucleus. In the first series of experiments, we examined NPY (or CART) fiber distribution within the boundary of adenosine deaminase (ADA)-immunoreactive (ir) TMN regions; extensive NPY (or CART)-ir axon terminals were observed in E4 (TMMd), E3 (TMMv), and E2 (TMVr) subdivisions. NPY varicosities co-contained vesicular GABA transporters (vGAT). CART boutons, however, contained either vGAT or vesicular glutamate transporters (vGLU), which suggested dual (or multiple) origins of CART fibers. Based on the previous observation on melanin-concentrating hormone (MCH)-ir neuronal elements in the TMN, their coexistence with CART peptide was examined in detail. In E subdivision, approximately 40.8% of MCH-ir somata co-contained CART, but the proportion was reduced to 24.1% in E region. In E and E (TMVc) regions, only MCH-ir axon terminals existed without any MCH-ir somata. In the second series of experiments, we investigated hypothalamic neuronal origin of NPY (or CART) fibers projecting to the TMN. The arcuate nucleus (Arc) was the sole source of hypothalamic NPY fibers projecting to the nucleus. In contrast, CART fibers in the TMN originated from the Arc as well as the other hypothalamic nuclei including the retrochiasmatic nucleus, paraventricular nucleus, lateral hypothalamus (LH), zona incerta (ZI), and dorsal hypothalamic area. Quantitative analysis showed that arcuate CART projection to the TMN occupied approximately 23.5% of the total hypothalamic CART input to the nucleus, while the rest originated mainly from the LH and ZI. The present observations suggested that the TMN might play a key role in energy balance and arousal, by receiving periphery-derived, first-order NPY (or CART) inputs from the Arc as well as second-order (and downstream) CART inputs from the other hypothalamic nuclei.
基于结节乳头体核（TMN）作为进食/觉醒相关功能靶点的重要性，我们在本研究中旨在探究投射至组胺能核的神经肽Y（NPY）和可卡因及苯丙胺调节转录肽（CART）纤维的下丘脑神经元起源。在第一组实验中，我们检查了腺苷脱氨酶（ADA）免疫反应性（ir）TMN区域边界内的NPY（或CART）纤维分布；在E4（TMMd）、E3（TMMv）和E2（TMVr）亚区观察到大量NPY（或CART）免疫反应性轴突终末。NPY曲张体共包含囊泡型GABA转运体（vGAT）。然而，CART终扣要么包含vGAT，要么包含囊泡型谷氨酸转运体（vGLU），这表明CART纤维有双重（或多重）起源。基于先前对TMN中黑色素浓集激素（MCH）免疫反应性神经元成分的观察，详细研究了它们与CART肽的共存情况。在E亚区，约40.8%的MCH免疫反应性胞体共包含CART，但在E区该比例降至24.1%。在E和E（TMVc）区，仅存在MCH免疫反应性轴突终末，没有任何MCH免疫反应性胞体。在第二组实验中，我们研究了投射至TMN的NPY（或CART）纤维的下丘脑神经元起源。弓状核（Arc）是投射至该核的下丘脑NPY纤维的唯一来源。相比之下，TMN中的CART纤维起源于Arc以及其他下丘脑核，包括视交叉后核、室旁核、外侧下丘脑（LH）、未定带（ZI）和下丘脑背侧区。定量分析表明，弓状核向TMN的CART投射约占下丘脑向该核的CART总输入的23.5%，而其余部分主要起源于LH和ZI。目前的观察结果表明，TMN可能通过接收来自Arc的外周来源的一级NPY（或CART）输入以及来自其他下丘脑核的二级（和下游）CART输入，在能量平衡和觉醒中发挥关键作用。
