Figure 8. Proposed mechanisms of the protective effect of exercise on METH-induced alterations of hippocampal neurogenesis.

METH disrupts TJ expression and localization in brain endothelial cells (ECs). In addition, METH increases the levels of inflammatory cytokines, such as IL-1β and TNF-α in plasma, which contribute to the disruption of the BBB integrity, leading to their entry into the brain. As a result of these events, differentiation of NPCs is impaired, which affects hippocampal neurogenesis. Exercise reverses these events by enhancing TJ protein expression and TJ assembly and by protecting against systemic induction of proinflammatory cytokines.