Zhang Jia, Fan Yan, Raza Muhammad U, Zhan Yanqiang, Du Xiang-Dong, Patel Paresh D, Zhu Meng-Yang
Departments of Biomedical Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States.
Department of Biochemistry, Nantong University College of Medicine, Nantong, China.
Neurochem Int. 2017 Sep;108:397-409. doi: 10.1016/j.neuint.2017.05.021. Epub 2017 May 31.
Our previous studies demonstrated that chronic social defeat (CSD) up-regulated expression of the serotonin transporter (SERT) and norepinephrine transporter (NET) in the brain, which was mediated by corticosteroid receptors. In the present study we first analyzed the alterations of corticosteroid receptors in different brain regions after the CSD paradigm. The results showed that CSD significantly reduced glucocorticoid receptor (GR) protein levels in the CA1 and dentate gyrus of the hippocampus, as well as in central and basolateral nuclei of the amygdala, which was accompanied by the translocation of GR from cytoplasm to nuclei. CSD also markedly reduced GR mRNA levels and MR immunoreactivity in the CA1, CA3 and dentate gyrus areas of the hippocampus. Conversely, CSD pronouncedly enhanced GR mRNA and protein levels in the dorsal raphe nucleus and locus coeruleus relative to the control. As an extension of our previous studies, in situ hybridization and immunohistochemical staining demonstrated that CSD regimen caused a notable increase of SERT mRNA levels in the dorsal raphe nucleus and increased SERT immunoreactivities in CA1 and CA3 of the hippocampus, as well as those in the basolateral nuclei of the amygdala. Likewise, CSD regimen resulted in an evident enhancement of NET immunoreactivity in the CA1 of the hippocampus and in the basolateral nuclei of the amygdala. Our current findings suggest that GR expressional alterations in response to CSD are complex and brain region-specific, which may correspond to their different functions in these regions.
我们之前的研究表明，慢性社会挫败（CSD）上调了大脑中血清素转运体（SERT）和去甲肾上腺素转运体（NET）的表达，这是由皮质类固醇受体介导的。在本研究中，我们首先分析了CSD范式后不同脑区皮质类固醇受体的变化。结果显示，CSD显著降低了海马体CA1区和齿状回以及杏仁核中央核和基底外侧核中的糖皮质激素受体（GR）蛋白水平，同时伴有GR从细胞质向细胞核的转位。CSD还显著降低了海马体CA1区、CA3区和齿状回区域的GR mRNA水平和盐皮质激素受体（MR）免疫反应性。相反，相对于对照组，CSD显著提高了中缝背核和蓝斑中的GR mRNA和蛋白水平。作为我们之前研究的延伸，原位杂交和免疫组织化学染色表明，CSD方案导致中缝背核中SERT mRNA水平显著增加，海马体CA1区和CA3区以及杏仁核基底外侧核中的SERT免疫反应性增加。同样，CSD方案导致海马体CA1区和杏仁核基底外侧核中NET免疫反应性明显增强。我们目前的研究结果表明，CSD引起的GR表达变化是复杂的且具有脑区特异性，这可能与其在这些区域的不同功能相对应。
