Sánchez M M, Young L J, Plotsky P M, Insel T R
Department of Psychiatry and Behavioral Sciences, and Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 30322,
J Neurosci. 2000 Jun 15;20(12):4657-68. doi: 10.1523/JNEUROSCI.20-12-04657.2000.
Chronic stress has been associated with degenerative changes in the rodent and primate hippocampus, presumably mediated in part via neuronal glucocorticoid receptors (GRs). In the rat brain, GRs are widely distributed and are particularly dense in the hippocampus. The distribution of GRs in the primate brain, however, has not been fully characterized. In this study, we used in situ hybridization histochemistry and immunohistochemistry to map the distribution of GR mRNA and GR protein, respectively, in adult rhesus monkeys (Macaca mulatta). In contrast to its well established distribution in the rat brain, GR mRNA was only weakly detected in the dentate gyrus (DG) and Cornu Ammonis (CA) of the macaque hippocampus, whereas it was abundant in the pituitary (PIT), cerebellum (CBL), hypothalamic paraventricular nucleus (PVN), and, to a lesser extent, the neocortex. Immunohistochemical staining indicated a very low density of GR-like immunoreactive cells within the macaque hippocampal formation in contrast to the high density observed within the PVN, prefrontal and entorhinal cortices, and cerebellar cortex. Relative to the low level of GR, mineralocorticoid receptor (MR) mRNA and protein expression were abundant within the DG and CA of the rhesus monkey hippocampal formation. These results indicate that, in the primate, neocortical and hypothalamic areas may be more important targets for GR-mediated effects of glucocorticoids than the hippocampus. Alternatively, it is also possible that glucocorticoid effects are mediated through the MRs present in the hippocampal formation.
慢性应激与啮齿动物和灵长类动物海马体的退行性变化有关,推测部分是通过神经元糖皮质激素受体(GRs)介导的。在大鼠脑中,GRs广泛分布,在海马体中尤其密集。然而,GRs在灵长类动物脑中的分布尚未完全明确。在本研究中,我们分别使用原位杂交组织化学和免疫组织化学方法,绘制成年恒河猴(猕猴)脑中GR mRNA和GR蛋白的分布图。与在大鼠脑中已确定的分布情况相反,在猕猴海马体的齿状回(DG)和海马角(CA)中仅微弱检测到GR mRNA,而在垂体(PIT)、小脑(CBL)、下丘脑室旁核(PVN)以及在较小程度上在新皮层中GR mRNA含量丰富。免疫组织化学染色显示,与在PVN、前额叶和内嗅皮层以及小脑皮层中观察到的高密度相比,猕猴海马结构内GR样免疫反应细胞的密度非常低。相对于GR的低水平,盐皮质激素受体(MR)mRNA和蛋白表达在恒河猴海马结构的DG和CA中丰富。这些结果表明,在灵长类动物中,新皮层和下丘脑区域可能比海马体更重要,是糖皮质激素通过GR介导作用的靶标。或者,糖皮质激素的作用也可能通过海马结构中存在的MRs介导。