EN
With a growing number of associations between daily activities and disease development, recent research has focused on understanding the contribution of lifestyle choices such as exercise. Several groups have demonstrated that exercise can improve activity, strength, aerobic capacity and emotional health. Our studies focused on the role of exercise in neurogenesis of neural progenitor cells (NPC) in the hippocampus in the context of the blood-brain barrier (BBB) integrity. The rationale is related to the fact that a substantial number of NPC are in direct proximity to the endothelium of brain microvessels, which form the BBB. The hippocampal dentate gyrus is an important site of adult neurogenesis, including the formation, survival, and integration of newly born neurons into the mature granule cell synaptic circuitry. Evidence indicates that adult hippocampal neurogenesis is important for learning and memory and is affected by disease conditions associated with cognitive impairment, depression, and anxiety. In a model of chronic methamphetamine administration, we observed decreased expression of tight junction proteins and increased BBB permeability in the hippocampus. These changes were associated with the development of significant aberrations of neural differentiation, such as a reduction in proliferating NPC and their conversion to neurons. Exercise protected against these effects by enhancing the expression of tight junction proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against methamphetamine-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate aberrant neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. FINANCIAL SUPPORT: This work was supported, in whole or in part, by NIH Grants DA039576, DA027569, HL126559, MH098891, and MH072567 as well as by NSC 2015/17/B/NZ7/02985