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小胶质细胞通过体细胞嘌呤能连接控制神经元发育。

Microglial control of neuronal development via somatic purinergic junctions.

机构信息

"Momentum" Laboratory of Neuroimmunology, Institute of Experimental Medicine, 1083 Budapest, Hungary.

"Momentum" Laboratory of Neuroimmunology, Institute of Experimental Medicine, 1083 Budapest, Hungary.

出版信息

Cell Rep. 2022 Sep 20;40(12):111369. doi: 10.1016/j.celrep.2022.111369.

Abstract

Microglia, the resident immune cells of the brain, play important roles during development. Although bi-directional communication between microglia and neuronal progenitors or immature neurons has been demonstrated, the main sites of interaction and the underlying mechanisms remain elusive. By using advanced methods, here we provide evidence that microglial processes form specialized contacts with the cell bodies of developing neurons throughout embryonic, early postnatal, and adult neurogenesis. These early developmental contacts are highly reminiscent of somatic purinergic junctions that are instrumental for microglia-neuron communication in the adult brain. The formation and maintenance of these junctions is regulated by functional microglial P2Y12 receptors, and deletion of P2Y12Rs disturbs proliferation of neuronal precursors and leads to aberrant cortical cytoarchitecture during development and in adulthood. We propose that early developmental formation of somatic purinergic junctions represents an important interface for microglia to monitor the status of immature neurons and control neurodevelopment.

摘要

小胶质细胞是大脑中的固有免疫细胞,在发育过程中发挥重要作用。虽然已经证明小胶质细胞与神经祖细胞或未成熟神经元之间存在双向通讯,但相互作用的主要部位和潜在机制仍不清楚。通过使用先进的方法,我们在这里提供证据表明,小胶质细胞突起与胚胎期、出生后早期和成年神经发生过程中发育中的神经元的细胞体形成专门的接触。这些早期发育接触非常类似于体细胞嘌呤能突触,对于成年大脑中小胶质细胞-神经元通讯至关重要。这些连接的形成和维持受功能小胶质细胞 P2Y12 受体的调节,P2Y12R 的缺失会干扰神经元前体的增殖,并导致发育过程中和成年期皮质细胞结构异常。我们提出,体细胞嘌呤能突触的早期发育形成代表了小胶质细胞监测未成熟神经元状态和控制神经发育的重要界面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b6f/9513806/7c8ce7dffee0/fx1.jpg

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