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神经精神疾病的星形胶质细胞关联:从星形细胞病变到星形胶质细胞增生。

Astroglial correlates of neuropsychiatric disease: From astrocytopathy to astrogliosis.

作者信息

Kim Ronald, Healey Kati L, Sepulveda-Orengo Marian T, Reissner Kathryn J

机构信息

Department of Psychology and Neuroscience, CB 3270, UNC Chapel Hill, Chapel Hill, NC 27599, United States.

Department of Psychology and Neuroscience, CB 3270, UNC Chapel Hill, Chapel Hill, NC 27599, United States..

出版信息

Prog Neuropsychopharmacol Biol Psychiatry. 2018 Dec 20;87(Pt A):126-146. doi: 10.1016/j.pnpbp.2017.10.002. Epub 2017 Oct 6.

Abstract

Complex roles for astrocytes in health and disease continue to emerge, highlighting this class of cells as integral to function and dysfunction of the nervous system. In particular, escalating evidence strongly implicates a range of changes in astrocyte structure and function associated with neuropsychiatric diseases including major depressive disorder, schizophrenia, and addiction. These changes can range from astrocytopathy, degeneration, and loss of function, to astrogliosis and hypertrophy, and can be either adaptive or maladaptive. Evidence from the literature indicates a myriad of changes observed in astrocytes from both human postmortem studies as well as preclinical animal models, including changes in expression of glial fibrillary protein, as well as changes in astrocyte morphology and astrocyte-mediated regulation of synaptic function. In this review, we seek to provide a comprehensive assessment of these findings and consequently evidence for common themes regarding adaptations in astrocytes associated with neuropsychiatric disease. While results are mixed across conditions and models, general findings indicate decreased astrocyte cellular features and gene expression in depression, chronic stress and anxiety, but increased inflammation in schizophrenia. Changes also vary widely in response to different drugs of abuse, with evidence reflective of features of astrocytopathy to astrogliosis, varying across drug classes, route of administration and length of withdrawal.

摘要

星形胶质细胞在健康和疾病中的复杂作用不断显现,凸显出这类细胞对神经系统功能和功能障碍的不可或缺性。特别是,越来越多的证据有力地表明,与包括重度抑郁症、精神分裂症和成瘾在内的神经精神疾病相关的星形胶质细胞结构和功能存在一系列变化。这些变化范围从星形胶质细胞病变、退化和功能丧失到星形胶质细胞增生和肥大,可能是适应性的,也可能是适应不良的。文献证据表明,在人类尸检研究以及临床前动物模型的星形胶质细胞中观察到无数变化,包括胶质纤维酸性蛋白表达的变化,以及星形胶质细胞形态和星形胶质细胞介导的突触功能调节的变化。在本综述中,我们试图对这些发现进行全面评估,并因此为与神经精神疾病相关的星形胶质细胞适应性的共同主题提供证据。虽然不同条件和模型的结果参差不齐,但总体发现表明,在抑郁症、慢性应激和焦虑症中,星形胶质细胞的细胞特征和基因表达减少,而在精神分裂症中炎症增加。对不同滥用药物的反应变化也很大,有证据表明,从星形胶质细胞病变到星形胶质细胞增生的特征各不相同,因药物类别、给药途径和戒断时间长短而异。

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