Paternal Exposure to Exercise and/or Caffeine and Alcohol Modify Offspring Behavioural and Pathophysiological Recovery from Repetitive Mild Traumatic Brain Injury (RmTBI) in Adolescence.

Only recently has the scope of parental research expanded to include the paternal sphere with epidemiological studies implicating stress, nutrition, and alcohol consumption in the neurobiological and behavioural characteristics of offspring. This study was designed to determine if paternal exposure to caffeine, alcohol, and exercise prior to conception would improve or exacerbate offspring recovery from adolescent repetitive mild traumatic brain injury (RmTBI). Sires received seven weeks of standard drinking water, or caffeine and ethanol, and were housed in regular cages or cages with running wheels, prior to being mated to control females. At postnatal day 40, offspring were administered RmTBI or sham injuries, and were assessed for post concussive symptomology. Post-mortem qRT-PCR was used to assess gene expression in the prefrontal cortex (PFC), nucleus accumbens (NAc), and changes in telomere length. Additionally, ELISAs were run on serum to detect levels of cytokines, chemokines, and sex hormones. Paternal experience did not improve or exacerbate RmTBI behavioural outcomes. However, female and male offspring displayed unique responses to RmTBI and paternal experience, resulting in changes in physical, behavioural, and molecular outcomes. Injury and paternal exercise modified changes in female offspring, whereas male offspring were affected by paternal exercise, caffeine, and alcohol treatment. Additionally, paternal experience and RmTBI modified expression of many genes in the PFC, NAc, telomere length, and levels of sex hormones. Although further exploration is required to understand the heterogeneity that exists in disease risk and resiliency, this study provides corroborating evidence that paternal experiences prior to conception influences offspring development.