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

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 postinjury and whether this differs between biological sexes is not well understood. In this study, we examined the microglial proteome at 3-, 7-, or 28-days after a midline fluid percussion injury (mFPI) in male and female mice using label-free quantitative proteomics. Data are available via ProteomeXchange with identifier PXD033628. 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 antiinflammatory function by 28 days following TBI. 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 proinflammation and phagocytosis as well as insulin and estrogen signaling in males compared with female mice that occurred with or without a brain injury. Although the microglial response was similar between males and females up to 28 days following TBI, biological sex differences in the microglial proteome, regardless of TBI, has implications for the efficacy of treatment strategies targeting the microglial response post-injury.

Research progress in the application of proteomics technology in brain injury

“…However, it is unclear whether the progression of microglial cell function over time after injury varies between biological genders (Xue et al, 2021). Therefore, Doust et al (2023) used label‐free LC–MS/MS omics technology to find out that at 3 and 7 days after injury, there was a decrease in microglial cell proteins that cleared neuronal debris through phagocytosis. Twenty‐eight days after injury, pro‐inflammatory proteins in microglia decreased and anti‐inflammatory proteins increased.…”