Pituitary adenylyl cyclase-activating polypeptide stimulates DNA synthesisbut delays maturation of oligodendrocyte progenitors

The neuropeptide pituitary adenylyl cyclase-activating peptide (PACAP) and one of its receptors (PAC(1)) are expressed in embryonic neural tube, where they appear to regulate neurogenesis and patterning. We now show that PAC( 1) gene expression is also present in neonatal rats in the ventricular and subventricular zones and in the optic chiasm, areas that are rich in oligod endrocyte (OL) progenitors (OLP). Because actions of PACAP on OLP have not been reported, we examined the effects of PACAP on the proliferation of pur ified OLP in culture and on myelinogenesis in cerebellar slices. Northern a nalyses on total RNA from purified glial cell subtypes revealed an abundant 7 kb hybridizing transcript in OLP, which was confirmed to correspond to t he PAC1 receptor by reverse transcription-PCR. The presence of this recepto r was also corroborated by radioligand binding and cAMP assay. In cultured OL, receptor density decreased during maturation but was partially counterb alanced by the appearance of sites that bound both PACAP and the related pe ptide vasoactive intestinal peptide. PACAP increased DNA synthesis in OLP c ultures almost twofold and increased the bromodeoxyuridine-labeling index i n O4-positive OLP. PACAP treatment also resulted in decreased sulfate incor poration into sulfatide in cultures of differentiating OL. The PACAP effect on sulfatide synthesis was fully reproduced in a cerebellar explant model. These findings indicate that PACAP may act at two stages during OL develop ment to (1) stimulate proliferation and (2) delay maturation and/or myelino genesis.