Vasoactive intestinal peptide (VIP) : control of hippocampal neurogenesis

Abstract

To understand the mechanisms underlying neuronal control of hippocampal neurogenesis, we are investigating the hypothesis that VIP modulates the activity of postnatal hippocampal stem/progenitor cells.

We have investigated VIP effects in hippocampal neuronal cultures from postnatal rats (P7-9).  BrdU and Ki-67 were used to measure cell proliferation. Quantification of cell death was achieved by DAPI and propidium iodide.  Immunohistochemistry was used to determine cell-specific phenotypes.  PCR assay was carried out to study the expression of VIP receptors.

We have shown that VIP at nanomolar concentrations has a trophic and self-renewal effect on nestin hippocampal cells in vitro, particularly the amplifying cell population, through enhanced symmetrical cell division.  This effect is specific for dentate gyrus progenitor cells.  Using immunohistochemistry and PCR techniques, we demonstrate the expression of VPAC1 and VPAC2 receptors and their mRNAs in hippocampal progenitor cultures.  Pharmacologically, we have shown that VIP survival and self-renewal effects are VPAC2 mediated.  We confirm that VPAC2 knockout adult mice have a significantly reduced number of newly-born neurons in the granule cell layer of the dentate gyrus.

We conclude that VIP is a trophic and self-renewal factor that may play a key role in hippocampal neurogenesis.  This work demonstrates a novel mechanism by which neuronal activity can influence trophism and fate of precursor cells in the hippocampus.

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