Paternal exposure to exercise and/or caffeine and alcohol modify offspring behavioral and pathophysiological recovery from repetitive mild traumatic brain injury in adolescence

Abstract

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 behavioral 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 7 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 quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to assess gene expression in the prefrontal cortex (PFC), nucleus accumbens (NAc) and changes in telomere length. Additionally, enzyme‐linked immunosorbent assay (ELISA's) were run on serum to detect levels of cytokines, chemokines and sex hormones. Paternal experience did not improve or exacerbate RmTBI behavioral outcomes. However, female and male offspring displayed unique responses to RmTBI and paternal experience, resulting in changes in physical, behavioral 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.

Developmental origins of health and disease: Impact of paternal nutrition and lifestyle

“…98 Also, reduced sensitivity to stress-induced hyperthermia is induced by PAE, selectively in male offspring. 97 Additionally, PAE negatively affects fetal growth in the male offspring to a greater extent than the females, and the growing deficits in males may persist into adult life with insulin hypersensitivity, increased markers of hepatic fibrosis, and alterations in immune signaling. 93 By contrast, the male offspring of alcohol-exposed sires are found resistant to HFD-induced obesity and improved glucose homeostasis via programmed increases in hepatic LXRα expression.…”

“…Female and male offspring display unique responses to repetitive mild traumatic brain injury and paternal experiences (exercise, caffeine, and alcohol), showing male instead of female offspring are affected by paternal alcohol treatment 98 . Also, reduced sensitivity to stress‐induced hyperthermia is induced by PAE, selectively in male offspring 97 . Additionally, PAE negatively affects fetal growth in the male offspring to a greater extent than the females, and the growing deficits in males may persist into adult life with insulin hypersensitivity, increased markers of hepatic fibrosis, and alterations in immune signaling 93 .…”

Repeated Mild Traumatic Brain Injury Causes Sex-specific Increases in Cell Proliferation and Inflammation in Juvenile Rats

“…Male performance is also worse with a prior history of concussion 21 , so manipulating timelines of inter-injury-intervals in repeated injury paradigms can be critical for teasing apart these heterogeneous outcomes. Indeed, signi cant sex differences from multiple injuries have been observed whether they occur in a single day [22][23][24] , 24-hours apart 25,26 , 48-hours apart 27,28 , 72-hours apart 29,30 , or 96-hours apart 31 .…”