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

AimsTo 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.

Automated summary

The study aims to investigate the phagocytosis of synapses by astrocytes in the ipsilateral hippocampus after traumatic brain injury (TBI). Through controlled cortical impact in mice, the researchers found a reduction in excitatory postsynaptic materials in the ipsilateral hippocampus during the subacute stage post-TBI, which was associated with cognitive dysfunction. They also identified phagocytic astrocytes containing secondary lysosomes wrapped around synapses and an increase in the co-location of GFAP and PSD-95, suggesting astrocytic engulfment of synaptic proteins. The study highlighted the role of Megf10 in astrocytic engulfment and its contribution to cognitive dysfunction following severe TBI in the CA1 region of the ipsilateral hippocampus.