少突胶质细胞祖细胞的分形因子依赖性小胶质细胞吞噬调节小脑白质发育

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-09-01 DOI:10.1016/j.isci.2025.113458

McKenzie K. Chappell , John Shelestak , Muhammad Irfan , Eric Shelestak , Ashley D. Nemes-Baran , Gabrielle M. Mey , Lakshmi Venkat , Amulya Surabhi , Tara M. DeSilva

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引用次数: 0

摘要

神经发育障碍通常包括运动和认知障碍，与大脑和小脑区域的成熟有关。本研究表明，在出生后早期发育过程中，变形样小胶质细胞通过第四脑室区浸润小脑白质，与大脑白质的类似活动平行。这些小胶质细胞在过渡到分支状态之前，在有限的时间窗口内吞噬少突胶质细胞祖细胞。裂肽受体信号的破坏（已知介导突触修剪）减少了小胶质OPC的吞噬，导致少突胶质细胞的增加和髓鞘发育的改变。fractalkine受体基因的变异与神经发育障碍有关，如自闭症和精神分裂症，这两种疾病都涉及髓磷脂异常。这些发现强调了变形虫小胶质细胞在形成大脑和小脑白质发育中的协调作用，表明这一过程的破坏可能导致神经发育障碍患者的脑回路和功能改变。

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$Cerebellar white matter development is regulated by fractalkine-dependent microglia phagocytosis of oligodendrocyte progenitor cells$

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Cerebellar white matter development is regulated by fractalkine-dependent microglia phagocytosis of oligodendrocyte progenitor cells

Neurodevelopmental disorders often involve both motor and cognitive impairments, linked to the maturation of cerebral and cerebellar regions. This study reveals that during early postnatal development, ameboid microglia infiltrate the cerebellar white matter via the fourth ventricular zone, in parallel with similar activity in the cerebral white matter. These microglia phagocytose oligodendrocyte progenitor cells (OPCs) within a restricted time window before transitioning to a ramified state. The disruption of fractalkine receptor signaling—known to mediate synaptic pruning—reduces microglial OPC engulfment, leading to an increase in oligodendrocytes and altered myelin development. Variants in the fractalkine receptor gene have been linked to neurodevelopmental disorders such as autism and schizophrenia, both of which involve myelin abnormalities. These findings highlight a coordinated role of ameboid microglia in shaping white matter development in both the cerebrum and cerebellum, suggesting that disruptions in this process may contribute to altered brain circuitry and function in neurodevelopmental disorders.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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