Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada; Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Cell Rep. 2021 Jan 5;34(1):108587. doi: 10.1016/j.celrep.2020.108587.
Despite a growing appreciation for microglial influences on the developing brain, the responsiveness of microglia to insults during gestation remains less well characterized, especially in the embryo when microglia themselves are still maturing. Here, we asked if fetal microglia could coordinate an innate immune response to an exogenous insult. Using time-lapse imaging, we showed that hypothalamic microglia actively surveyed their environment by near-constant "touching" of radial glia projections. However, following an insult (i.e., IUE or AAV transduction), this seemingly passive touching became more intimate and long lasting, ultimately resulting in the retraction of radial glial projections and degeneration into small pieces. Mechanistically, the TAM receptors MERTK and AXL were upregulated in microglia following the insult, and Annexin V treatment inhibited radial glia breakage and engulfment by microglia. These data demonstrate a remarkable responsiveness of embryonic microglia to insults during gestation, a critical window for neurodevelopment.
尽管人们越来越认识到小胶质细胞对发育中大脑的影响，但在妊娠期间，小胶质细胞对损伤的反应仍然不太清楚，尤其是在胚胎时期，小胶质细胞本身仍在成熟。在这里，我们想知道胎儿小胶质细胞是否能够协调对外部损伤的先天免疫反应。使用延时成像，我们发现下丘脑小胶质细胞通过对放射状胶质细胞突起的近乎持续的“接触”，积极地探测周围环境。然而，在受到损伤（即 IUE 或 AAV 转导）后，这种看似被动的接触变得更加密切和持久，最终导致放射状胶质细胞突起回缩并退化成小块。从机制上讲，TAM 受体 MERTK 和 AXL 在损伤后在小胶质细胞中上调，并且 Annexin V 处理抑制了小胶质细胞对放射状胶质细胞的断裂和吞噬。这些数据表明，胚胎小胶质细胞在妊娠期间对损伤具有显著的反应性，这是神经发育的关键窗口。
