Repeated mild traumatic brain injuries in mice cause age- and sex-specific alterations in dendritic spine density

Abstract

Mild traumatic brain injuries (mTBI) plague the human population and their prevalence is increasing annually. More so, repeated mTBIs (RmTBI) are known to manifest and compound neurological deficits in vulnerable populations. Age at injury and sex are two important factors influencing RmTBI pathophysiology, but we continue to know little about the specific effects of RmTBI in youth and females. In this study, we directly quantified the effects of RmTBI on adolescent and adult, male and female mice, with a closed-head lateral impact model. We report age- and sex-specific neurobehavioural deficits in motor function and working memory, microglia responses to injury, and the subsequent changes in dendritic spine density in select brain regions. Specifically, RmTBI caused increased footslips in adult male mice as assessed in a beam walk assay and significantly reduced the time spent with a novel object in adolescent male and female mice. RmTBIs caused a significant reduction in microglia density in male mice in the motor cortex, but not female mice. Finally, RmTBI significantly reduced dendritic spine density in the agranular insular cortex (a region of the prefrontal cortex in mice) and increased dendritic spine density in the adolescent male motor cortex. Together, the data provided in this study sheds new light on the heterogeneity in RmTBI-induced behavioural, glial, and neuronal architecture changes dependent on age and sex.