Involvement of VIP on BDNF-induced somatostatin gene expression in cultured fetal rat cerebral cortical cells

Previous studies have shown that BDNF promotes expression of SS. In earlier studies we demonstrated the stimulatory effect of locally produced VIP upo n SS secretion. These facts led us to explore the peptidergic action of BDN F on VIP, and to determine if BDNF-induced SS might be mediated by the indu ction of VIP. Cultured fetal rat cerebralcortical cells were incubated with BDNF (50 ng/ml) and/or VIP (10(-11) M) for 2 and 5 days. In other experime nts I-Gs from BDNF or VIP antisera were also added. BDNF increased VIP and SS gene expression and peptide production. After 2 days of incubation with both BDNF and VIP the induction of SS mRNA was similar to that obtained wit h BDNF alone. However when the treatment was extended to 5 days the increas e in SS mRNA was higher than that obtained with BDNF alone. This finding su ggests the possibility that both factors acted synergistically. To define t he potential role of VIP in the response of SS gene expression to BDNF, end ogenous VIP was blocked with IgGs from VIP antiserum. Under these experimen tal conditions BDNF-induced SS decreased. Our study provides the first evid ence that BDNF up-regulates VIP gene expression and concentration of the pe ptide. The involvement of VIP on BDNF-induced SS gene expression is also de monstrated. (C) 2001 Elsevier Science B.V. All rights reserved.