Repetitive concussions promote microglia-mediated engulfment of presynaptic excitatory input associated with cognitive dysfunction

反复脑震荡促进小胶质细胞介导的与认知功能障碍相关的突触前兴奋性输入的吞噬

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作者:Maryam Chahin, Julius Mutschler #, Stephanie P Dzhuleva #, Clara Dieterle, Leidy Reyes Jimenez, Srijan Raj Bhattarai, Valerie Van Steenbergen, Florence M Bareyre

Abstract

Concussions are a current health concern and account for the vast majority of head trauma. While symptoms after a single impact are usually transient, repetitive concussions, as often occur in sports, are responsible for persistent acute and chronic deficits. Here, we used a model of bilateral midline-centered concussions in mice to show that repetitive concussions selectively induce impairments in learning ability compared to single-impact injuries. Since microglial cells and their activation are considered key factors in degenerative pathology after brain trauma, we examined their structure and function after single and repetitive concussions in the cortex underlying the concussions and in the hippocampus. We found that only repetitive concussions led to a significant long-lasting structural activation of microglia and an increase in microglia-mediated engulfment of presynaptic excitatory synapses, while the elimination of inhibitory synapses was not altered. Since the density of excitatory input did not change during the 6-week study period, we hypothesize that there is a turnover of excitatory synapses following repetitive concussion that can be compensated for, anatomically but not behaviorally.

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