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bioRxiv · 10.1101/2022.05.01.490239

Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics

Doust, Y.·Bindoff, A.·Holloway, O.·Wilson, R.·King, A.·Ziebell, J.
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Abstract

Traumatic brain injury (TBI) triggers neuroinflammatory cascades mediated by microglia, which promotes tissue repair in the short-term. These cascades may exacerbate TBI-induced tissue damage and symptoms in the months to years post-injury. However, the progression of the microglial function across time post-injury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome in the days (3- and 7-days) to 1 month (28 days) after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. We identified a reduction in microglial proteins involved with clearance of neuronal debris via phagocytosis at 3- and 7-days post-injury. At 28 days post-injury pro-inflammatory proteins were decreased and anti-inflammatory proteins were increased in microglia. These results indicate a reduction in microglial clearance of neuronal debris in the days post-injury with a shift to anti-inflammatory function by 1 month. The changes in the microglial proteome that occurred across time post-injury did not differ between biological sexes. However, we did identify an increase in microglial proteins related to pro-inflammation as well as insulin and estrogen signalling in males compared with female mice that occurred with or without a brain injury. Although microglial response was similar between males and females up to 1 month following TBI, biological sex differences in the basal microglial proteome has implications for the efficacy of treatment strategies targeting the microglial response post-injury.

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Doust, Y., Bindoff, A., Holloway, O., Wilson, R., King, A., Ziebell, J.. 2022-05-02. Temporal changes in the microglial proteome of male and female mice after a diffuse brain injury using label-free quantitative proteomics. https://doi.org/10.1101/2022.05.01.490239

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