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

李晨1 ,葛海龙1 ,黄俊洁1 ,谢银平2 ,王高华1

神经损伤与功能重建 ›› 2026, Vol. 21 ›› Issue (7) : 373-380.

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神经损伤与功能重建 ›› 2026, Vol. 21 ›› Issue (7) : 373-380. DOI: 10.16780/j.cnki.sjssgncj.20241251
论著

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

  • 李晨1 ,葛海龙1 ,黄俊洁1 ,谢银平2 ,王高华1
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Elevated FKBP51 in the Hippocampus is Involved in Susceptibility to Chronic UnpredictableMild Stress in Male Rats

  • LI Chen1 ,GE Hailong1 ,HUANG Junjie1 ,XIE Yinping2 ,WANG Gaohua1
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摘要

目的:探究海马、前额叶皮质及下丘脑中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、前额叶皮质及下丘脑组织,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表达及其在细胞内的分布。结论:海马中上调的FKBP51可能通过影响神经元活性和GR 表达及其细胞内分布参与雄性大鼠对CUMS的易感性。

Abstract

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.

关键词

抑郁症;FKBP51;糖皮质激素受体;慢性不可预测温和应激

Key words

depressive disorder; FKBP51; glucocorticoid receptor; chronic unpredictable mild stress (CUMS)

引用本文

导出引用
李晨1 ,葛海龙1 ,黄俊洁1 ,谢银平2 ,王高华1. 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[J]. 神经损伤与功能重建. 2026, 21(7): 373-380 https://doi.org/10.16780/j.cnki.sjssgncj.20241251
LI Chen1 ,GE Hailong1 ,HUANG Junjie1 ,XIE Yinping2 ,WANG Gaohua1. Elevated FKBP51 in the Hippocampus is Involved in Susceptibility to Chronic UnpredictableMild Stress in Male Rats[J]. Neural Injury and Functional Reconstruction. 2026, 21(7): 373-380 https://doi.org/10.16780/j.cnki.sjssgncj.20241251

基金

国家自然科学基金 (HSP90通过LAMP2A 调控伴侣蛋白 介导自噬诱导铁死 亡在抑郁症发生中 的可能机制研究, No. 82071523);武 汉大学腾飞计划(神 经科学疾病与功能 协同创新研究,No. TFLC2018001);湖 北省重点研发项目 (新冠肺炎创伤后 应激障碍 PTSD 发 病机制与智能化精 准防治,No. 2020B CA064)

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