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小胶质细胞维持着发育中的额突迁移流中的稳态条件。

Microglia Maintain Homeostatic Conditions in the Developing Rostral Migratory Stream.

机构信息

Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520.

Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520.

出版信息

eNeuro. 2023 Feb 8;10(2). doi: 10.1523/ENEURO.0197-22.2023. Print 2023 Feb.

Abstract

Microglia invade the neuroblast migratory corridor of the rostral migratory stream (RMS) early in development. The early postnatal RMS does not yet have the dense astrocyte and vascular scaffold that helps propel forward migrating neuroblasts, which led us to consider whether microglia help regulate conditions permissive to neuroblast migration in the RMS. GFP-labeled microglia in mice assemble primarily along the outer borders of the RMS during the first postnatal week, where they exhibit predominantly an ameboid morphology and associate with migrating neuroblasts. Microglia ablation for 3 d postnatally does not impact the density of pulse labeled BrdU+ neuroblasts nor the distance migrated by tdTomato electroporated neuroblasts in the RMS. However, microglia wrap DsRed-labeled neuroblasts in the RMS of P7 mice and express the markers CD68, CLEC7A, MERTK, and IGF-1, suggesting active regulation in the developing RMS. Microglia depletion for 14 d postnatally further induced an accumulation of CC3+ DCX+ apoptotic neuroblasts in the RMS, a wider RMS and extended patency of the lateral ventricle extension in the olfactory bulb. These findings illustrate the importance of microglia in maintaining a healthy neuroblast population and an environment permissive to neuroblast migration in the early postnatal RMS.

摘要

小胶质细胞在发育早期就侵入了头侧迁移流(RMS)的神经母细胞迁移通道。新生后早期的 RMS 尚未形成有助于推动向前迁移的神经母细胞的密集星形胶质细胞和血管支架,这促使我们考虑小胶质细胞是否有助于调节 RMS 中神经母细胞迁移的条件。在新生后第一周,GFP 标记的小胶质细胞主要聚集在 RMS 的外边界,表现出主要的阿米巴样形态,并与迁移的神经母细胞相关。新生后 3 天小胶质细胞消融不会影响脉冲标记 BrdU+神经母细胞的密度,也不会影响 tdTomato 电穿孔神经母细胞在 RMS 中的迁移距离。然而,小胶质细胞在 P7 小鼠的 RMS 中包裹 DsRed 标记的神经母细胞,并表达标记物 CD68、CLEC7A、MERTK 和 IGF-1,表明在发育中的 RMS 中存在活跃的调节。新生后 14 天小胶质细胞耗竭进一步导致 RMS 中 CC3+DCX+凋亡神经母细胞的积累、RMS 更宽以及嗅球侧脑室延伸的通畅性延长。这些发现说明了小胶质细胞在维持早期新生 RMS 中健康的神经母细胞群体和有利于神经母细胞迁移的环境中的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b71/9910579/204686f4edbe/ENEURO.0197-22.2023_f011.jpg

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