Hippocampal interneurons are direct targets for circulating glucocorticoids.
Hippocampal interneurons are direct targets for circulating glucocorticoids.
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DOI：
10.1002/cne.25322
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发表时间：
2022-08
影响因子：
2.5
通讯作者：
Danzer, Steve C.
中科院分区：
文献类型：
--
作者：
Kraus, Kimberly L.;Chordia, Arihant P.;Drake, Austin W.;Herman, James P.;Danzer, Steve C.
近年来，海马由于其在认知功能、神经病理学和下丘脑-垂体-肾上腺（HPA）轴调节中的作用而成为应激研究的重要靶点。尽管压力对精神和神经系统疾病的普遍影响，但引起边缘系统对压力反应的调节的许多回路和细胞依赖性机制仍然未知。海马兴奋性神经元通常表达高水平的糖皮质激素受体（GR），因此定位为直接响应血清糖皮质激素。反过来，这些神经元又受到邻近的中间神经元的调节，这些中间神经元的亚型已被证明对压力暴露做出反应。然而，GR在海马中间神经元中的表达还没有得到很好的表征。为了确定关键的中间神经元群体是否是糖皮质激素作用的直接靶点，我们利用两个转基因小鼠系来标记小白蛋白（PV+）和生长抑素（SST+）阳性中间神经元。标记的中间神经元的GR免疫染色的特点是在背侧和腹侧齿状门，齿状细胞体层，和CA 1和CA 3层的oriens和stratum的。虽然几乎所有的海马SST+ interneurons在所有区域表达GR，GR标记的PV+ interneurons显示出相当大的亚区变异性。PV+、GR+细胞的百分比在CA 3皮层中最高，在CA 1皮层中最低，其他区域显示中等水平的表达。总之，这些发现表明，在基线条件下，海马SST+中间神经元是普遍存在的糖皮质激素靶点，而只有不同的PV+中间神经元群体是直接靶点。这种解剖学上的多样性表明应激依赖性海马反应调节的功能差异。在背侧和腹侧海马亚区（CA 1，CA 3，DG）和细胞层中，GR蛋白阳性的海马小白蛋白（PV）阳性和生长抑素（SST）阳性中间神经元的百分比。
The hippocampus has become a significant target of stress research in recent years because of its role in cognitive functioning, neuropathology, and regulation of the hypothalamic pituitary adrenal (HPA) axis. Despite the pervasive impact of stress on psychiatric and neurological disease, much of the circuit- and cell-dependent mechanisms giving rise to the limbic regulation of the stress response remain unknown. Hippocampal excitatory neurons generally express high levels of glucocorticoid receptors (GRs) and are therefore positioned to respond directly to serum glucocorticoids. These neurons are, in turn, regulated by neighboring interneurons, subtypes of which have been shown to respond to stress exposure. However, GR expression among hippocampal interneurons is not well characterized. To determine whether key interneuron populations are direct targets for glucocorticoid action, we utilized two transgenic mouse lines to label parvalbumin (PV+) and somatostatin (SST+)-positive interneurons. GR immunostaining of labeled interneurons was characterized within the dorsal and ventral dentate hilus, dentate cell body layer, and CA1 and CA3 stratum oriens and stratum pyramidale. While nearly all hippocampal SST+ interneurons expressed GR across all regions, GR labeling of PV+ interneurons showed considerable subregion variability. The percentage of PV+, GR+ cells was highest in CA3 stratum pyramidale, and lowest in CA1 stratum oriens, with other regions showing intermediate levels of expression. Together, these findings indicate that, under baseline conditions, hippocampal SST+ interneurons are a ubiquitous glucocorticoid target, while only distinct populations of PV+ interneurons are direct targets. This anatomical diversity suggests functional differences in the regulation of stress-dependent hippocampal responses. Percentage of hippocampal parvalbumin (PV)-positive and somatostatin (SST)-positive interneurons which are positive for GR protein across dorsal and ventral hippocampal subregions (CA1, CA3, DG) and cell layers.
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