Moderate Exercise Stimulates PACAP-Mediated Neurogenesis in Rat Dentate Gyrus and Cerebellar Cortex.

Background

Moderate physical activity (PA) exerts powerful systemic and neuroprotective effects, reducing chronic disease risk and enhancing cognitive and psychological well-being. PA promotes brain plasticity by upregulating neurotrophic factors and stimulating neurogenesis. Given the established role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in neuronal survival, differentiation, and anti-apoptotic signaling, we aimed to investigate whether moderate PA modulates the endogenous expression of PACAP and its specific receptor PAC1R in the DG and cerebellar cortex.

Methods

To this end, twenty-four rats were distributed into sedentary or exercise groups. Immunohistochemical and Western blot analyses were performed to assess PACAP and PAC1R expression. Co-expression with doublecortin (DCX), a marker of immature neurons, was evaluated to explore the direct relationship between PACAP signaling and neurogenesis.

Results

Our results showed that moderate PA induced a significant up-regulation of PACAP and PAC1R in both the DG and cerebellar cortex compared to sedentary controls. Moreover, high co-expression of PACAP and DCX was detected in these regions, suggesting an involvement of PACAP in exercise-induced neurogenic processes.

Conclusions

These findings demonstrate that moderate physical activity is associated with enhanced PACAP/PAC1R signaling and DCX expression in neurogenic regions, warranting further investigation into its specific contribution to exercise-induced brain plasticity.