Megf10‐related engulfment of excitatory postsynapses by astrocytes following severe brain injury

Author:

Zhuang Yuan1,Xu Xiaojian2,Li Hao1,Niu Fei2,Yang Mengshi1,Ge Qianqian1,Lu Shenghua1,Deng Yu1,Wu Hongbin1,Zhang Bin3,Liu Baiyun1245ORCID

Affiliation:

1. Department of Neurosurgery, Beijing Tiantan Hospital Capital Medical University Beijing China

2. Beijing Key Laboratory of Central Nervous System Injury Beijing Neurosurgical Institute, Capital Medical University Beijing China

3. Department of Intensive Care Unit, Beijing Tiantan Hospital Capital Medical University Beijing China

4. Center for Nerve Injury and Repair Beijing Institute of Brain Disorders Beijing China

5. China National Clinical Research Center for Neurological Diseases Beijing China

Abstract

AbstractAimsTo investigate astrocyte‐related phagocytosis of synapses in the ipsilateral hippocampus after traumatic brain injury (TBI).MethodsWe performed controlled cortical impact to simulate TBI in mice. Seven days postinjury, we performed cognitive tests, synapse quantification, and examination of astrocytic phagocytosis in association with Megf10 expression.ResultsDuring the subacute stage post‐TBI, we found a reduction in excitatory postsynaptic materials in the ipsilateral hippocampus, which was consistent with poor performance in the cognitive test. The transcriptome data suggested that robust phagocytosis was responsible for this process. Coincidently, we identified phagocytic astrocytes containing secondary lysosomes that were wrapped around the synapses in the ipsilateral hippocampus. Moreover, a significant increase in the co‐location of GFAP and PSD‐95 in the CA1 region suggested astrocytic engulfment of excitatory postsynaptic proteins. After examining the reported phagocytic pathways, we found that both the transcription level and protein expression of Megf10 were elevated. Co‐immunofluorescence of GFAP and Megf10 demonstrated that the expression of Megf10 was spatially upregulated in astrocytes, exclusively in the CA1 region, and was related to the astrocytic engulfment of PSD‐95.ConclusionOur study elaborated that the Megf10‐related astrocytic engulfment of PSD‐95 in the CA1 region of the ipsilateral hippocampus aggravated cognitive dysfunction following severe TBI.

Funder

National Natural Science Foundation of China

Publisher

Wiley

Subject

Pharmacology (medical),Physiology (medical),Psychiatry and Mental health,Pharmacology

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