Exercise normalizes altered expression of proteins in the ventral hippocampus of rats subjected to maternal separation

Many studies have reported on the detrimental effects of early life adversity and the beneficial effects of exercise on brain function. However, the molecular mechanisms that underpin these various effects remain poorly understood. The advent of advanced proteomic analysis techniques has enabled simultaneous measurement of protein expression in a wide range of biological systems. We therefore used iTRAQ proteomic analysis of protein expression to determine whether exercise counteracts the detrimental effects of early life adversity in the form of maternal separation on protein expression in the brain. Rat pups were subjected to maternal separation from postnatal day 2 to 14 for 3 h day(-1) or normally reared. At 40 days of age, half of the rats in each group (maternal separation and normally reared) were allowed to exercise voluntarily (access to a running wheel) for 6 weeks and the remainder kept as sedentary control animals. At 83 days of age, rats were killed and the ventral hippocampus was dissected for quantitative proteomic (iTRAQ) analysis. The iTRAQ proteomic analysis identified several proteins that had been altered by maternal separation, including proteins involved in neuronal structure, metabolism, signalling, anti-oxidative stress and neurotransmission, and that many of these proteins were restored to normal by subsequent exposure to voluntary exercise in adolescence. Our data show that a broad range of proteins play a role in the complex consequences of adversity and exercise.