한빛사논문
Youkyeong Gloria Byun,1,2,5 Nam-Shik Kim,1,2,5 Gyuri Kim,1,2,5 Yi-Seon Jeon,1,3 Jong Bin Choi,1,2,4 Chan-Woo Park,1,2 Kyungdeok Kim,1,3 Hyunsoo Jang,1,2 Jinkyeong Kim,1,3 Eunjoon Kim,1,3 Yong-Mahn Han,1,2,4 Ki-Jun Yoon,1,2 Seung-Hee Lee,1,3 and Won-Suk Chung1,2,6,*
1Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
2KAIST Stem Cell Center, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
3Center for Synaptic Brain Dysfunctions, Institute for Basic Science, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea
4Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Republic of Korea
5These authors contributed equally
6Lead contact
*Corresponding author: correspondence to Won-Suk Chung
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.
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