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

Marissa Sgro; Zoe N Kodila; Crystal Li; Irena Carmichael; Samantha Warren; Amy C Reichelt; Glenn R Yamakawa; Richelle Mychasiuk

doi:10.1016/j.isci.2024.109395

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

iScience. 2024 Mar 2;27(4):109395. doi: 10.1016/j.isci.2024.109395. eCollection 2024 Apr 19.

Authors

Marissa Sgro¹, Zoe N Kodila¹, Crystal Li¹, Irena Carmichael², Samantha Warren², Amy C Reichelt³, Glenn R Yamakawa¹, Richelle Mychasiuk¹

Affiliations

¹ Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
² Monash Micro Imaging, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
³ School of Biomedicine, University of Adelaide, Adelaide, SA 5005, Australia.

Abstract

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.

Keywords: Microbiome; Neuroscience.