Axotomy-induced changes in pituitary adenylate cyclase activating polypeptide (PACAP) and PACAP receptor gene expression in the adult rat facial motor nucleus

It has been demonstrated that pituitary adenylate cyclase activating polype ptide (PACAP) promotes the survival of neurons in culture and can inhibit n euronal cell death after experimental injury. Furthermore, peripheral axoto my results in increased PACAP gene expression in sensory and sympathetic ne urons, suggesting that PACAP might be a mediator in the injury response in certain parts of the nervous system. However, changes in PACAP expression h ave not been reported in injured motor neurons, despite the significant pro blem of motor neuron degeneration in injury and in several neurological dis eases. We examined here changes in gene expression of PACAP and two high-af finity PACAP receptors, PAC(1) and VPAC(2), in adult rat motor neurons afte r facial nerve axotomy by in situ hybridization. PACAP gene expression was very low in facial motor neurons of normal rats. However, a robust time-dep endent increase in PACAP mRNA was observed in the facial motor nucleus in m ost or all axotomized motor neurons. This induction was detectable 6 hr aft er axotomy, and peaked at 48 hr, when expression on the injured side averag ed more than 20-fold higher than that on the contralateral side. Thereafter , PACAP mRNA levels decreased slightly, but remained more than 10-fold elev ated for as long as 30 days after axotomy. In contrast to PACAP, gene expre ssion for both the PAC1 and VPAC2 receptor was high in facial motor neurons of normal rats. No significant change was observed for VPAC2 receptor gene expression in facial motor neurons after axotomy, whereas gene expression for the PAC1 receptor became significantly decreased. The results indicate that the PACAP ligand receptor system is tightly regulated in the facial mo tor nucleus after axotomy, providing evidence that PACAP may be involved in motor injury responses. (C) 1999 Wiley-Liss, Inc.