Microbiome depletion prior to repeat mild TBI differentially alters social deficits and prefrontal cortex plasticity in adolescent and adult rats.

Although aging, repeat mild traumatic brain injury (RmTBI), and microbiome modifications independently change social behavior, there has been no investigation into their cumulative effects on social behavior and neuroplasticity within the prefrontal cortex. Therefore, we examined how microbiome depletion prior to RmTBI affected social behavior and neuroplasticity in adolescent and adult rats. Play, temperament analysis, elevated plus maze, and the hot/cold plate assessed socio-emotional function. Analyses of perineuronal nets (PNNs) and parvalbumin (PV) interneurons was completed. Social-emotional deficits were more pronounced in adults, with microbiome depletion attenuating social behavior deficits associated with RmTBI in both age groups. Microbiome depletion increased branch length and PNN arborization within the PFC but decreased the overall number of PNNs. Adults and males were more vulnerable to RmTBI. Interestingly, microbiome depletion may have attenuated the changes to neuroplasticity and subsequent social deficits, suggesting that the microbiome is a viable, but age-specific, target for RmTBI therapeutics.