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| 海马中上调的FKBP51参与雄性大鼠对慢性不可预测温和应激的易感性 |
| Elevated FKBP51 in the hippocampus is involved in susceptibility to chronic unpredictable mild stress in male rats |
| 投稿时间：2025-02-18 修订日期：2025-02-18 |
| DOI： |
| 中文关键词: 抑郁症，FKBP51，糖皮质激素受体，慢性不可预测温和应激 |
| 英文关键词: depressive disorder, FKBP51, glucocorticoid receptor, chronic unpredictable mild stress (CUMS) |
| 基金项目:国家自然科学基金（82071523）；武汉大学腾飞计划（TFLC2018001）；湖北省重点研发项目（2020BCA064） |
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| 中文摘要: |
| 目的：探究海马、前额叶皮层及下丘脑中FK506结合蛋白51（FK506 binding protein 51，FKBP51）表达量与雄性大鼠对慢性不可预测温和应激（Chronic unpredictable mild stress，CUMS）的易感性是否相关及其可能机制。方法：雄性SD大鼠随机分为对照组和CUMS组。根据4周CUMS后的行为学结果，将暴露于CUMS的大鼠分为易感和抵抗两组。取海马、前额叶皮层及下丘脑组织，检测FKBP51和糖皮质激素受体（Glucocorticoid receptor，GR）的表达。将海马中FKBP51和GR表达量与大鼠抑郁样行为进行相关性分析。检测海马区域神经元活性，在PC12细胞中检测GR在核内外的表达。结果：与对照组相比，CUMS易感组大鼠的海马中FKBP51 mRNA和蛋白表达增加，同时GR mRNA和蛋白表达减少，而CUMS抵抗组没有显著差异。大鼠的抑郁样行为和海马中FKBP51的表达量呈正相关。此外，升高的FKBP51可能影响神经元活性和GR表达及其在胞内的分布。结论：海马中上调的FKBP51可能通过影响神经元活性和GR表达及其胞内分布参与雄性大鼠对CUMS的易感性。 |
| 英文摘要: |
| Objective: To investigate whether the expression of FK506 binding protein 51 (FKBP51) in the hippocampus, prefrontal cortex and hypothalamus regions is associated with susceptibility to chronic unpredictable mild stress (CUMS) in male rats and to elucidate the underlying mechanisms. Methods: Male SD rats were randomly subjected into control and CUMS groups. After four-week CUMS, rats exposed to CUMS were divided into susceptible and resistant groups based on the results of behavioral tests. Then, tissue samples were obtained from the hippocampus, prefrontal cortex, and hypothalamus to ascertain the expression of FKBP51 and glucocorticoid receptor (GR). Furthermore, the linear correlations between depressive behaviors and hippocampal FKBP51 expression in rats were analyzed. Subsequently, hippocampal neurogenesis was detected, and cytosolic and nuclear GR expression was observed in PC12 cells. Results: Compared with the control group, CUMS-susceptible rats exhibited elevated FKBP51 mRNA and protein levels and decreased GR mRNA and protein levels in the hippocampus, whereas there was no significant difference in the CUMS-resistant groups. The depressive behavior in rats was found to be positively correlated with expression of FKBP51 in the hippocampus. Additionally, elevated FKBP51 may affected neuron activity and the expression and intracellular distribution of GR. Conclusion: The elevated FKBP51 in the hippocampus may be involved in susceptibility to CUMS in male rats by affecting neuron activity and GR expression and its intracellular distribution. |
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