Hippocampal neurogenesis occurs throughout life in mammals and has pivotal roles in brain functions. An enriched environment stimulates hippocampal neurogenesis, but the exact mechanisms are still unclear. The present study investigated the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in adult hippocampal neurogenesis under standard or enriched rearing conditions. Rearing in the enriched conditions from 4-weeks old for 4-weeks increased the survival of newly divided cells in the subgranular zone and granule cell layer of the dentate gyrus of wild-type and PACAP-knockout (PACAP-/-) mice. The increase in the survival in the granule cell layer was less in PACAP-/- mice than in the wild-type mice. In contrast, the proliferation of newly divided cells in mice reared in the standard and enriched conditions did not differ between the wild-type and PACAP-/- mice. Regarding the differentiation of newborn cells in the dentate gyrus, most of the newly divided cells exhibited the neuronal phenotype in both the wild-type and PACAP-/- mice under standard and enriched conditions. These findings suggest that endogenous PACAP is partly involved in the survival of the enriched environment-induced generation, but not in the basal rate, of newborn cells in the dentate gyrus of the adult hippocampus.
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