Despite their known roles in regulating food intake, appetite, satiety, and social behavior, the roles of vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in hippocampal neuronal cell development remain unclear. Therefore, the aim was to evaluate the effect of VIP and PACAP on 1) the proliferation of a hippocampal cell line, 2) the number of neurons and astrocytes in primary hippocampal cell culture, and 3) the morphology of primary hippocampal neurons. It was found that both VIP (100 nM) and PACAP (100 nM) stimulated the proliferation of E2 hippocampal cells over a 72-hour period. A significant increase in the number of NeuN-positive primary hippocampal neurons was observed following VIP incubation on day in vitro (DIV) 9. An increase in GFAP-positive cells following PACAP incubation was observed from DIV3 compared to DIV5, DIV7, and DIV9. PACAP significantly inhibited the growth of short neurites in primary hippocampal neurons. In conclusion, this study demonstrates that both neuropeptides VIP and PACAP influence the proliferation and growth of hippocampal neuronal cells, with PACAP having a more pronounced effect on astrocyte numbers and reducing neurite branching. These findings emphasize the role of VIP and PACAP in the hippocampus during early brain development.
