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

## TL;DR

Moderate exercise increases PACAP and PAC1R in rat brain regions linked to new neuron growth.

## Contribution

This study identifies PACAP-mediated neurogenesis as a novel mechanism through which exercise promotes brain plasticity.

## Key findings

- Moderate exercise upregulates PACAP and PAC1R in the dentate gyrus and cerebellar cortex.
- PACAP co-expresses with DCX, indicating a role in exercise-induced neurogenesis.

## Abstract

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.