精神疾病患者前额皮质中糖皮质激素受体共激活因子 FKBP5、BAG1 和 PTGES3 的失调。
Dysregulation of glucocorticoid receptor co-factors FKBP5, BAG1 and PTGES3 in prefrontal cortex in psychotic illness.
机构信息
1] Schizophrenia Research Institute, Sydney, New South Wales, Australia [2] Neuroscience Research Australia, Sydney, New South Wales, Australia [3] School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia [4] Neuropsychiatric Signaling Program, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania.
1] Schizophrenia Research Institute, Sydney, New South Wales, Australia [2] Neuroscience Research Australia, Sydney, New South Wales, Australia [3] School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia.
出版信息
Sci Rep. 2013 Dec 18;3:3539. doi: 10.1038/srep03539.
Molecular abnormalities within the glucocorticoid receptor (GR) stress signaling pathway may confer, or reflect, susceptibility to stress in schizophrenia and bipolar disorder, but the extent of such abnormalities in the brain is not known. Using RNA-Seq and qPCR in two postmortem cohorts totaling 55 schizophrenia, 34 bipolar disorder and 55 control individuals, we identified increased FKBP5 and PTGES3 mRNA expression, and decreased BAG1 mRNA expression, in the prefrontal cortex in schizophrenia cases relative to controls (68.0% [p < 0.001], 26.0% [p < 0.01] and 12.1% [p < 0.05] respectively). We also observed increased FKBP5 and decreased BAG1 mRNA expression in bipolar disorder (47.5% [p < 0.05] and 14.9% [p < 0.005]). There were no diagnostic differences in steady-state FKBP51 protein levels, nor in HSPA1A, HSP90AA1, DNAJB1 or HSPB1 mRNA levels. GR, co-factor and chaperone mRNA levels were strongly correlated. These results reveal coordinated cortical dysregulation of FKBP5, PTGES3, BAG1 and GR genes within the glucocorticoid signaling pathway in psychotic illness.
糖皮质激素受体 (GR) 应激信号通路中的分子异常可能导致精神分裂症和双相情感障碍的易感性，或反映这种易感性，但大脑中这种异常的程度尚不清楚。我们使用 RNA-Seq 和 qPCR 在两个总计 55 例精神分裂症、34 例双相情感障碍和 55 例对照个体的死后队列中发现，与对照组相比，精神分裂症病例的前额叶皮层中 FKBP5 和 PTGES3 mRNA 的表达增加，而 BAG1 mRNA 的表达减少（分别为 68.0% [p < 0.001]、26.0% [p < 0.01] 和 12.1% [p < 0.05]）。我们还观察到双相情感障碍中 FKBP5 增加和 BAG1 mRNA 减少（分别为 47.5% [p < 0.05] 和 14.9% [p < 0.005]）。FKBP51 蛋白水平、HSPA1A、HSP90AA1、DNAJB1 或 HSPB1 mRNA 水平在诊断上没有差异。GR、共因子和伴侣蛋白 mRNA 水平呈强相关。这些结果揭示了在精神疾病中糖皮质激素信号通路中 FKBP5、PTGES3、BAG1 和 GR 基因的皮质协同失调。
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