Notter Tina
Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK.
Brain Neurosci Adv. 2021 Apr 27;5:23982128211009148. doi: 10.1177/23982128211009148. eCollection 2021 Jan-Dec.
Schizophrenia is a severe and clinically heterogenous mental disorder affecting approximately 1% of the population worldwide. Despite tremendous achievements in the field of schizophrenia research, its precise aetiology remains elusive. Besides dysfunctional neuronal signalling, the pathophysiology of schizophrenia appears to involve molecular and functional abnormalities in glial cells, including astrocytes. This article provides a concise overview of the current evidence supporting altered astrocyte activity in schizophrenia, which ranges from findings obtained from post-mortem immunohistochemical analyses, genetic association studies and transcriptomic investigations, as well as from experimental investigations of astrocyte functions in animal models. Integrating the existing data from these research areas strongly suggests that astrocytes have the capacity to critically affect key neurodevelopmental and homeostatic processes pertaining to schizophrenia pathogenesis, including glutamatergic signalling, synaptogenesis, synaptic pruning and myelination. The further elucidation of astrocytes functions in health and disease may, therefore, offer new insights into how these glial cells contribute to abnormal brain development and functioning underlying this debilitating mental disorder.
精神分裂症是一种严重且临床异质性的精神障碍,全球约1%的人口受其影响。尽管精神分裂症研究领域取得了巨大成就,但其确切病因仍不清楚。除了神经元信号传导功能失调外,精神分裂症的病理生理学似乎还涉及胶质细胞(包括星形胶质细胞)的分子和功能异常。本文简要概述了目前支持精神分裂症中星形胶质细胞活性改变的证据,这些证据来自尸检免疫组织化学分析、基因关联研究和转录组学研究的结果,以及动物模型中星形胶质细胞功能的实验研究。整合这些研究领域的现有数据强烈表明,星形胶质细胞有能力严重影响与精神分裂症发病机制相关的关键神经发育和稳态过程,包括谷氨酸能信号传导、突触形成、突触修剪和髓鞘形成。因此,进一步阐明星形胶质细胞在健康和疾病中的功能,可能会为这些胶质细胞如何导致这种使人衰弱的精神障碍背后的异常大脑发育和功能提供新的见解。