Wheel running attenuates microglia proliferation and increases expression of a proneurogenic phenotype in the hippocampus of aged mice.

Aging is associated with low-grade neuroinflammation including primed microglia that may contribute to deficits in neural plasticity and cognitive function. The current study evaluated whether exercise modulates division and/or activation state of microglia in the dentate gyrus of the hippocampus, as activated microglia can express a classic inflammatory or an alternative neuroprotective phenotype. We also assessed hippocampal neurogenesis to determine whether changes in microglia were associated with new neuron survival. Adult (3.5 months) and aged (18 months) male BALB/c mice were individually housed with or without running wheels for 8 weeks. Mice received bromodeoxyuridine injections during the first or last 10 days of the experiment to label dividing cells. Immunofluorescence was conducted to measure microglia division, co-expression of the neuroprotective indicator insulin-like growth factor (IGF-1), and new neuron survival. The proportion of new microglia was increased in aged mice, and decreased from wheel running. Running increased the proportion of microglia expressing IGF-1 suggesting exercise shifts microglia phenotype towards neuroprotection. Additionally, running enhanced survival of new neurons in both age groups. Findings suggest that wheel running may attenuate microglia division and promote a proneurogenic phenotype in aged mice.