Opposing effects of positive and negative stress on hippocampal plasticity over the lifespan.

Early developmental experience shapes neuronal circuits and influences the trajectory of cognitive aging. Just as adversity early in life can accelerate age-related synaptic impairments, enhancement of neuronal metabolism and function in the developing brain could potentially protect neurons against the synaptic consequences of aging. In this regard, metabolic enhancements following exercise directly oppose the deleterious consequences of adverse stress. In this review, we examine the relationship between exercise and other forms of stress over the lifespan. Exercise is a specialized form of stress in that it is predictable and voluntary, while other forms of psychological and physiological stress are unpredictable and uncontrollable, with distinct consequences for behavior and synaptic plasticity. Themes emerging from the literature surrounding the opposing effects of adversity and exercise include epigenetic mechanisms that converge on the regulation of neurotrophic factor expression and neurogenesis. These data suggest that exercise-induced neuroprotection and neuronal endangerment following adversity may both be transferable across generations, in a manner that has the potential to impact neuroplasticity over the lifespan.