压力通过增加星形胶质细胞中噬菌受体MERTK的表达，促进突触噬菌作用，导致行为异常的发生。
Stress induces behavioral abnormalities by increasing expression of phagocytic receptor, MERTK, in astrocytes to promote synapse phagocytosis.
发表日期：2023 Jul 26
作者：
Youkyeong Gloria Byun, Nam-Shik Kim, Gyuri Kim, Yi-Seon Jeon, Jong Bin Choi, Chan-Woo Park, Kyungdeok Kim, Hyunsoo Jang, Jinkyeong Kim, Eunjoon Kim, Yong-Mahn Han, Ki-Jun Yoon, Seung-Hee Lee, Won-Suk Chung
来源：
IMMUNITY
摘要：
儿童忽视和/或虐待可能引发未知机制的心理健康问题。在此，我们确定了压力激素作为星形胶质细胞介导的突触吞噬强力诱导剂。通过体外、体内和人脑器官体实验，我们证明了压力激素通过糖皮质激素受体（GR）增加了星形胶质细胞中Mertk吞噬受体的表达。在新生小鼠中，早期社交剥夺（ESD）暴露特异性激活了星形胶质细胞中的GR-MERTK信号通路，但并未激活小胶质细胞。在ESD小鼠的皮层区，兴奋性突触密度降低，且星形胶质细胞吞噬这些突触的程度增加。通过去除星形胶质细胞中的GR或MERTK，我们基本预防了ESD小鼠中兴奋性突触的丢失、异常神经网络活动和行为异常。我们的研究揭示了星形胶质细胞GR-MERTK激活在引发压力诱导的小鼠异常行为中的关键作用，暗示了GR-MERTK信号通路作为压力诱导的心理健康问题的治疗靶点。版权所有©2023 The Authors. Published by Elsevier Inc. All rights reserved.
Childhood neglect and/or abuse can induce mental health conditions with unknown mechanisms. Here, we identified stress hormones as strong inducers of astrocyte-mediated synapse phagocytosis. Using in vitro, in vivo, and human brain organoid experiments, we showed that stress hormones increased the expression of the Mertk phagocytic receptor in astrocytes through glucocorticoid receptor (GR). In post-natal mice, exposure to early social deprivation (ESD) specifically activated the GR-MERTK pathway in astrocytes, but not in microglia. The excitatory post-synaptic density in cortical regions was reduced in ESD mice, and there was an increase in the astrocytic engulfment of these synapses. The loss of excitatory synapses, abnormal neuronal network activities, and behavioral abnormalities in ESD mice were largely prevented by ablating GR or MERTK in astrocytes. Our work reveals the critical roles of astrocytic GR-MERTK activation in evoking stress-induced abnormal behaviors in mice, suggesting GR-MERTK signaling as a therapeutic target for stress-induced mental health conditions.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.