Involvement of endogenous PACAP expression in the activity-dependent survival of mouse cerebellar granule cells

Membrane depolarization causes Ca2+ influx through L-type voltage-dependent calcium channels (L-VDCC), which promotes the activity-dependent survival of mouse cerebellar granule cells (CGCs). Although exogenously added pituit ary adenylate cyclase activating polypeptide (PACAP) is effective: in promo ting the survival of CGCs, it is unknown whether PACAP is synthesized in CG Cs and involved in the activity-dependent survival of CGCs. In this study. we found that the PACAP gene was activated in depolarized CGCs cultured at 25 mM KC1 thigh K+). independently of de novo protein synthesis. In additio n, the PACAP immunoreactivity increased through the activation of L-VDCC in depolarized CGCs, indicating that PACAP is concomitantly produced with PAC AP mRNA in an activity-dependent manner. Exogenously added PACAP attenuated the apoptosis of CGCs through a specific interaction with PACAP receptors. Furthermore, a PACAP receptor antagonist. PACAP(6-38), reduced the surviva l of CGCs at high K-1. These findings indicate that endogenous PACAP produc tion induced by Ca signals exerts a survival effect on CGCs via PACAP recep tors, which. at least in part, accounts for the activity-dependent survival of CGCs. (C) 2001 Published by Elsevier Science Ireland Ltd and the Japan Neuroscience Society. All rights reserved..