title: Ontogeny of PACAP receptors in the human cerebellum: perspectives of therapeutic applications.
abstract: It is now well established that pituitary adenylate cyclase-activating polypeptide (PACAP) exerts anti-apoptotic and pro-differentiating actions during development of the rodent cerebellum. Cell signaling involved in the neurotrophic effects of PACAP has been precisely investigated. In particular, PACAP is a potent inhibitor of the mitochondrial apoptotic pathway through an ERK- and PKA-dependent mechanism. However, transposition of the neurodevelopmental activities of PACAP to the human cerebellum remains speculative, essentially because of the lack of data concerning the PACAP-ergic system. The present review is based on recent results that provide the first molecular, pharmacological and anatomical characterizations of PACAP receptors in the developing human cerebellum. It is now clearly established that the distribution pattern of PAC1-R and VPAC1-R mRNA in the human cerebellum is very similar to that already described in rodents. [(125)I]PACAP27 binding sites are closely associated with germinative neuroepithelia in fetal stages and with mature granule cells in infants and adults. Pharmacological characterization revealed that, in fetuses, PACAP binding sites exhibit a PAC1-R profile while, in adult patients, they correspond to a heterogeneous population of PAC1-R and VPAC(1/2)-R. Altogether, these data provide the first evidence that PACAP may exert neurodevelopmental functions in the human cerebellum.
authors.affiliation: INSERM U413, IFRMP 23, University of Rouen, 76821 Mont Saint Aignan, France.
authors.forename: Magali
authors.initials: M
authors.lastname: Basille
authors.forename: Anthony
authors.initials: A
authors.lastname: Falluel-Morel
authors.forename: David
authors.initials: D
authors.lastname: Vaudry
authors.forename: Nicolas
authors.initials: N
authors.lastname: Aubert
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Pierre
authors.initials: P
authors.lastname: Fréger
authors.forename: Nicole
authors.initials: N
authors.lastname: Gallo-Payet
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Bruno
authors.initials: B
authors.lastname: Gonzalez
mesh_terms: D002531:Cerebellum / Q000378:metabolism*; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D012333:RNA, Messenger; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide