Neurotrophic activity of pituitary adenylate cyclase-activating polypeptide on rat cerebellar cortex during development
AUTOR(ES)
Vaudry, David
FONTE
The National Academy of Sciences
RESUMO
High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) receptors are present in the external granule cell layer of the rat cerebellum during postnatal development. In vitro studies have shown that PACAP promotes cell survival and neurite outgrowth on immature cerebellar granule cells in primary culture. In the present study, we have investigated the effect of PACAP on the development of the cerebellar cortex of 8-day-old rats. Incubation of cultured granule cells for 12 or 18 h with PACAP provoked a significant increase in the rate of incorporation of [3H]thymidine in cultured granule cells, suggesting that PACAP could stimulate the proliferation of granule cells. After 96 h of treatment, in vivo administration of PACAP provoked a transient increase in the number of granule cells in the molecular layer and in the internal granule cell layer. In contrast, PACAP did not affect the number of Purkinje cells. The augmentation of the number of granule cells evoked by PACAP was significantly inhibited by the PACAP receptor antagonist PACAP(6–38). Administration of PACAP also caused a significant increase in the volume of the cerebellar cortex. The present study provides evidence that PACAP can act in vivo as a trophic factor during rat brain development. Our data indicate that PACAP increases proliferation and/or inhibits programmed cell death of granule cells, as well as stimulating neuronal migration from the external granule cell layer toward the internal granule cell layer.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=17797Documentos Relacionados
- Pituitary adenylate cyclase-activating polypeptide protects rat cerebellar granule neurons against ethanol-induced apoptotic cell death
- Altered psychomotor behaviors in mice lacking pituitary adenylate cyclase-activating polypeptide (PACAP)
- The pituitary adenylate cyclase–activating polypeptide is a physiological inhibitor of platelet activation
- Anti-inflammatory role in septic shock of pituitary adenylate cyclase-activating polypeptide receptor
- Molecular cloning and functional expression of the pituitary adenylate cyclase-activating polypeptide type I receptor.