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

Akiko Tabuchi, Motoko Koizumi, Jun Nakatsubo, Takahiro Yaguchi, Masaaki Tsuda*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

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 pituitary adenylate cyclase activating polypeptide (PACAP) is effective in promoting the survival of CGCs, it is unknown whether PACAP is synthesized in CGCs 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 KCl (high K+), independently of de novo protein synthesis. In addition, the PACAP immunoreactivity increased through the activation of L-VDCC in depolarized CGCs, indicating that PACAP is concomitantly produced with PACAP 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 survival of CGCs at high K+. These findings indicate that endogenous PACAP production induced by Ca2+ signals exerts a survival effect on CGCs via PACAP receptors, which, at least in part, accounts for the activity-dependent survival of CGCs.

Original languageEnglish
Pages (from-to)85-93
Number of pages9
JournalNeuroscience Research
Volume39
Issue number1
DOIs
StatePublished - 2001

Keywords

  • Apoptosis
  • Ca channel
  • Calcium
  • Cell survival
  • Cerebellar granule cells
  • Gene expression
  • PACAP

ASJC Scopus subject areas

  • General Neuroscience

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