Center for Animal Genomics, Veterinary Faculty, University of Ljubljana, Slovenia.
Exp Neurol. 2011 Dec;232(2):176-84. doi: 10.1016/j.expneurol.2011.08.021. Epub 2011 Aug 30.
The ventromedial nucleus of the hypothalamus (VMH) is a key cell group in the medial-basal hypothalamus that participates in the regulation of energy balance. Previous studies have shown that the cellular organization of the VMH is altered in mice with a disruption of the steroidogenic factor-1 (NR5a1) gene (SF-1 KO mice). The present study examined orexigenic/anorexigenic peptides (neuropeptide Y (NPY), agouti-related peptide (AgRP) and cocaine- and amphetamine-regulated transcript (CART)) and neural connections to and from the VMH in SF1 KO mice. NeuroVue tracing and Golgi staining were used to evaluate connections between the preoptic area (POA) and VMH and the orientation of dendrites in the VMH, respectively. Results of this study reveal changes in the cytoarchitecture of the region of the VMH with respect to the distribution of immunoreactive NPY, AgRP and CART. In WT mice projections from the POA normally surround the VMH while in SF-1 KO mice, projections from the POA stream through the region that would otherwise be VMH. Golgi impregnation of the region revealed fewer dendrites with ventrolateral orientations and in general, more variable dendritic orientations in SF-1 KO mice providing additional evidence that the connectivity of cells in the region is likely altered due to the cellular rearrangements consequent to disruption of the NR5a1 gene. In conclusion, this study greatly extends the data showing that the morphology of the regions containing the VMH is disrupted in SF-1 KO mice and suggests that changes in the location of cells or fibers containing NPY, AgRP and CART may, in part, account for changes in body weight homeostasis in these mice.
下丘脑腹内侧核（VMH）是内侧基底下丘脑的关键细胞群，参与能量平衡的调节。先前的研究表明，类固醇生成因子-1（NR5a1）基因（SF-1 KO 小鼠）破坏的小鼠中 VMH 的细胞组织发生改变。本研究检查了食欲肽/厌食肽（神经肽 Y（NPY）、刺鼠相关肽（AgRP）和可卡因和安非他命调节转录物（CART））以及 VMH 与 VMH 之间的神经连接。NeuroVue 示踪和高尔基染色分别用于评估视前区（POA）与 VMH 之间的连接以及 VMH 中树突的方向。这项研究的结果揭示了 VMH 区域的细胞结构发生了变化，与免疫反应性 NPY、AgRP 和 CART 的分布有关。在 WT 小鼠中，来自 POA 的投射通常环绕 VMH，而在 SF-1 KO 小鼠中，来自 POA 的投射穿过原本是 VMH 的区域。VMH 区域的高尔基浸渍显示出较少的具有腹外侧取向的树突，并且通常在 SF-1 KO 小鼠中具有更多变化的树突取向，这提供了额外的证据表明，由于破坏 NR5a1 基因导致的细胞重新排列，该区域细胞的连接可能发生改变。总之，这项研究大大扩展了数据，表明 SF-1 KO 小鼠中包含 VMH 的区域的形态被破坏，并表明 NPY、AgRP 和 CART 所含细胞或纤维的位置变化可能部分解释了这些小鼠体重平衡的变化。
