韩国先进科技学院Won-Suk Chung研究组揭示应激通过增加星形胶质细胞中吞噬受体MERTK的表达，促进突触吞噬，从而诱导行为异常。2023年7月31日出版的《免疫》发表了这项成果。

他们发现应激激素是星形胶质细胞介导的突触吞噬的强诱导剂。通过体外、体内和人脑类器官实验，他们发现应激激素通过糖皮质激素受体(glucocorticoid receptor, GR)增加星形胶质细胞Mertk吞噬受体的表达。在出生后小鼠中，暴露于早期社会剥夺(ESD)特异性激活星形胶质细胞中的GR-MERTK通路，但在小胶质细胞中没有。ESD小鼠皮层区兴奋性突触后密度降低，这些突触的星形细胞吞噬增加。

通过消融星形胶质细胞中的GR或MERTK, ESD小鼠的兴奋性突触丧失、神经网络活动异常和行为异常在很大程度上得到了预防。他们的工作揭示了星形细胞GR-MERTK激活在小鼠应激诱导异常行为中的关键作用，提示GR-MERTK信号是应激诱导精神健康状况的治疗靶点。

研究人员表示，儿童期忽视和/或虐待可导致机制未知的精神健康状况。

附：英文原文

Title: Stress induces behavioral abnormalities by increasing expression of phagocytic receptor, MERTK, in astrocytes to promote synapse phagocytosis

Author: 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

Issue&Volume: 2023-07-31

Abstract: 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.

DOI: 10.1016/j.immuni.2023.07.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00318-7