Fekete Csaba, Wittmann Gábor, Liposits Zsolt, Lechan Ronald M
Department of Endocrine and Behavioral Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary.
J Comp Neurol. 2004 Feb 9;469(3):340-50. doi: 10.1002/cne.10999.
Axons containing cocaine- and amphetamine-regulated transcript (CART) densely innervate the hypothalamic paraventricular nucleus (PVN). Recent data from our laboratory demonstrated that CART-immunoreactive (IR) neurons of arcuate nucleus origin innervate the PVN, but comprise only a portion of the total CART-IR input to this region of the brain. To identify sources other than the arcuate nucleus, retrograde transport studies were performed with cholera toxin B subunit (CTB), focally delivered into the PVN of adult rats. Neurons double-labeled for CTB and CART were visualized by immunofluorescence. The most prominent groups of double-labeled cells were identified in the retrochiasmatic area, arcuate nucleus, lateral hypothalamus, perifornical area, zona incerta, C1-3 regions, and the medial subnucleus of the nucleus tractus solitarius (NTS). In addition, scattered retrogradely labeled CART-IR neurons were found in the parabrachial nucleus. In the diencephalon, the majority of double-labeled neurons were localized ipsilateral to the injection site; however, in the medulla the CART/CTB-containing neurons were found bilaterally. By triple-labeling immunofluorescence, CART/CTB neurons in the perifornical area, zona incerta complex, and more medial portions of the lateral hypothalamus were found to co-contain melanin concentrating hormone (MCH), whereas CART/CTB neurons of the C1-3 regions of the brainstem but not medial subnucleus of the NTS were observed to express phenylethanolamine N-methyltransferase (PNMT). We conclude that the CART innervation of the PVN derives from multiple neuronal sources of the hypothalamus and medulla. These observations raise the possibility that CART serves multiple functions in the PVN and is utilized to transmit diverse physiological signals that contribute to the complex regulation of homeostatic functions of the PVN.
含有可卡因和苯丙胺调节转录物（CART）的轴突密集地支配下丘脑室旁核（PVN）。我们实验室最近的数据表明，源自弓状核的CART免疫反应性（IR）神经元支配PVN，但仅占该脑区总CART-IR输入的一部分。为了确定弓状核以外的来源，用霍乱毒素B亚单位（CTB）进行逆行运输研究，将其局部注入成年大鼠的PVN。通过免疫荧光观察到CTB和CART双标记的神经元。在视交叉后区、弓状核、下丘脑外侧区、穹窿周区、未定带、C1-3区和孤束核内侧亚核（NTS）中发现了最突出的双标记细胞群。此外，在臂旁核中发现了散在的逆行标记的CART-IR神经元。在间脑中，大多数双标记神经元位于注射部位的同侧；然而，在延髓中，含CART/CTB的神经元双侧存在。通过三重标记免疫荧光，发现穹窿周区、未定带复合体和下丘脑外侧区更内侧部分的CART/CTB神经元共含有黑色素浓缩激素（MCH），而脑干C1-3区而非NTS内侧亚核的CART/CTB神经元表达苯乙醇胺N-甲基转移酶（PNMT）。我们得出结论，PVN的CART神经支配来自下丘脑和延髓的多个神经元来源。这些观察结果增加了CART在PVN中发挥多种功能的可能性，并被用于传递多种生理信号，这些信号有助于PVN稳态功能的复杂调节。
