NPY augments the proliferative effect of FGF2 and increases the expression of FGFR1 on nestin positive postnatal hippocampal precursor cells, via the Y1 receptor

Abstract

We have shown that neuropeptide Y (NPY), a peptide neurotransmitter released by hippocampal interneurons, is proliferative for hippocampal neural stem progenitor cells (NSPCs) via the Y1 receptor. Fibroblast growth factor (FGF) 2, released predominantly by astrocytes, is also a powerful mitogen for postnatal and adult NSPCs, via the FGFR1 receptor. Knockout studies show that NPY and FGF2 are individually necessary, but not sufficient, for seizure-induced neurogenesis, suggesting a possible interaction. Here, we examined for interactions between NPY and FGF2 on NSPCs from the postnatal hippocampus and report that the combination of NPY and FGF2 significantly shortens the cell cycle time of nestin positive NSPCs, more than either factor alone. This augmentation of proliferation rate is NPY Y1 receptor mediated, and Y1 receptor activation increases both FGFR1 mRNA and protein in NSPC cultures. NSPCs immunostain for both Y1 and FGFR1 receptors and the interaction is specific for dentate NSPCs. This is the first report of a proliferative factor that augments the proliferative effect of FGF2 and is the first evidence of a positive proliferative interaction between a glial growth factor and a neuronal transmitter, identifying a novel neural activity driven mechanism for modulating the proliferation of hippocampal NSPCs.