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Volume 17, Number 1, Issue of January 1, 1997 pp. 83-90
Copyright ©1997 Society for NeurosciencePituitary Adenylate Cyclase-Activating Polypeptide (PACAP-38) Protects Cerebellar Granule Neurons from Apoptosis by Activating the Mitogen-Activated Protein Kinase (MAP Kinase) Pathway
Received Aug. 12, 1996; revised Sept. 30, 1996; accepted Oct. 8, 1996.
Martin Villalba, Joël Bockaert, and Laurent Journot Centre National de la Recherche Scientifique (CNRS), Unité Propre de Recherche 9023, Centre CNRS-Institut National de la Santé et de la Recherche Médicale de Pharmacologie-Endocrinologie, F-34094 Montpellier Cedex 05, France
Pituitary adenylate cyclase-activating polypeptides (PACAP-27 and PACAP-38) are neuropeptides of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon family. PACAP receptors are expressed in different brain regions, including cerebellum. We used primary culture of rat cerebellar granule neurons to study the effect of PACAP-38 on apoptosis induced by potassium deprivation. We demonstrated that PACAP-38 increased survival of cerebellar neurons in a dose-dependent manner by decreasing the extent of apoptosis estimated by DNA fragmentation. PACAP-38 induced activation of the extracellular signal-regulated kinase (ERK)-type of mitogen-activated protein (MAP) kinase through a cAMP-dependent pathway. PD98059, an inhibitor of MEK (MAP kinase kinase), completely abolished the antiapoptotic effect of PACAP-38, suggesting that MAP kinase pathway activation is necessary for PACAP-38 action.
Key words: PACAP; cerebellum; apoptosis; MAP kinase; cAMP; PD 98059
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