Dallaporta M, Pecchi E, Pio J, Jean A, Horner K C, Troadec J D
Département de Physiologie Neurovégétative, Centre de recherche en Neurobiologie-Neurophysiologie de Marseille (CRN2M), Université Paul Cézanne, Marseille, France.
J Neuroendocrinol. 2009 Jan;21(1):57-67. doi: 10.1111/j.1365-2826.2008.01799.x.
Leptin, an adipocyte-derived hormone, regulates food intake and body weight by acting principally on the hypothalamus, which displays the highest expression of leptin receptor (Ob-R). Nevertheless, other regions of the brain express Ob-R and constitute leptin's target sites. The dorsal vagal complex (DVC), an integrative centre of autonomic functions located in the caudal brainstem, is one of these structures. Leptin, by acting through the DVC, affects autonomic and neuroendocrine functions, such as control of food intake and gastric motility. In the present study, we observed Ob-R labelling within the DVC in cells that correspond to neuronal cell bodies. We showed for the first time Ob-R expression in a subpopulation of glial fibrillary acid protein positive cells located at the border between the area postrema and the nucleus tractus solitarius (NTS). These glial cells exhibit an atypical morphology consisting of unbranched processes that radiate rostro-caudally from the fourth ventricle wall. In vitro, the glial cells exhibited both long and short Ob-R expression with a preferential expression of the Ob-Ra and-f isoforms. Interestingly, using i.v and i.c.v. injection of the fluorescent tracer hydroxystilbamidine, we provided evidence that these cells may constitute a diffusion barrier which might regulate entry of molecules into the NTS. Finally, modulation of energy status, by acute or chronic reduction of food intake, modulated especially the short Ob-R isoforms in the DVC. In the light of these results, we hypothesise that Ob-R positive glial cells of the DVC participate in the transport of leptin into the brainstem and thus contribute to regulation of energy homeostasis.
瘦素是一种由脂肪细胞分泌的激素,主要通过作用于下丘脑来调节食物摄入和体重,而下丘脑表达最高水平的瘦素受体(Ob-R)。然而,大脑的其他区域也表达Ob-R并构成瘦素的靶位点。背侧迷走神经复合体(DVC)是位于脑干尾部的自主神经功能整合中心,就是其中之一。瘦素通过作用于DVC,影响自主神经和神经内分泌功能,如对食物摄入和胃动力的控制。在本研究中,我们在与神经元细胞体相对应的DVC细胞内观察到Ob-R标记。我们首次在位于最后区和孤束核(NTS)边界的胶质纤维酸性蛋白阳性细胞亚群中显示了Ob-R的表达。这些胶质细胞呈现出非典型形态,由从第四脑室壁向头尾方向辐射的无分支突起组成。在体外,这些胶质细胞同时表现出长型和短型Ob-R表达,且优先表达Ob-Ra和-f亚型。有趣的是,通过静脉注射和脑室内注射荧光示踪剂羟基二苯乙烯脒,我们证明这些细胞可能构成一个扩散屏障,调节分子进入NTS。最后,通过急性或慢性减少食物摄入量来调节能量状态,特别调节了DVC中的短型Ob-R亚型。鉴于这些结果,我们推测DVC中Ob-R阳性胶质细胞参与瘦素向脑干的转运,从而有助于能量稳态的调节。