期刊
SCHIZOPHRENIA BULLETIN
卷 -, 期 -, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/schbul/sbad065
关键词
oligodendrocytes; oligodendrocyte precursor cells; myelination; cognition; hippocampus; prefrontal cortex
类别
There is a disconnectivity between hippocampal and prefrontal brain regions in schizophrenia, which leads to cognitive impairment. The deficient maturation of oligodendrocyte precursor cells (OPCs) contributes to abnormal frontotemporal connectivity and cognitive deficits in schizophrenia. Aerobic exercise training can increase hippocampal volume, specifically in the CA4 region, and improve cognition in individuals with schizophrenia. The exercise-induced CA4 volume increase is significantly correlated with OPCs.
Background and Hypothesis Cognitive impairment is a hallmark of schizophrenia, but no effective treatment is available to date. The underlying pathophysiology includes disconnectivity between hippocampal and prefrontal brain regions. Supporting evidence comes from diffusion-weighted imaging studies that suggest abnormal organization of frontotemporal white matter pathways in schizophrenia. Study Design Here, we hypothesize that in schizophrenia, deficient maturation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes substantially contributes to abnormal frontotemporal macro- and micro-connectivity and subsequent cognitive deficits. Study Results Our postmortem studies indicate a reduced oligodendrocyte number in the cornu ammonis 4 (CA4) subregion of the hippocampus, and others have reported the same histopathological finding in the dorsolateral prefrontal cortex. Our series of studies on aerobic exercise training showed a volume increase in the hippocampus, specifically in the CA4 region, and improved cognition in individuals with schizophrenia. The cognitive effects were subsequently confirmed by meta-analyses. Cell-specific schizophrenia polygenic risk scores showed that exercise-induced CA4 volume increase significantly correlates with OPCs. From animal models, it is evident that early life stress and oligodendrocyte-related gene variants lead to schizophrenia-related behavior, cognitive deficits, impaired oligodendrocyte maturation, and reduced myelin thickness. Conclusions Based on these findings, we propose that pro-myelinating drugs (e.g., the histamine blocker clemastine) combined with aerobic exercise training may foster the regeneration of myelin plasticity as a basis for restoring frontotemporal connectivity and cognition in schizophrenia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据