Opposite regulation of calbindin and calretinin expression by brain-derived neurotrophic factor in cortical neurons

Regulation of calbindin and calretinin expression by brain-derived neurotro phic factor (BDNF) was examined in primary cultures of cortical neurons usi ng immunocytochemistry and northern blot analysis. Here we report that regu lation of calretinin expression by BDNF is in marked contrast to that of ca lbindin. Indeed, chronic exposure of cultured cortical neurons for 5 days t o increasing concentrations of BDNF (0.1-10 ng/ml) resulted in a concentrat ion-dependent decrease in the number of calretinin-positive neurons and a c oncentration-dependent increase in the number of calbindin-immunoreactive n eurons. Consistent with the immunocytochemical analysis, BDNF reduced calre tinin mRNA levels and up-regulated calbindin mRNA expression, providing evi dence that modifications in gene expression accounted for the changes in th e number of calretinin- and calbindin-containing neurons, Among other membe rs of the neurotrophin family, neurotrophin-4 (NT-4), which also acts by ac tivating tyrosine kinase TrkB receptors, exerted effects comparable to thos e of BDNF, whereas nerve growth factor (NGF) was ineffective. As for BDNF a nd NT-4, incubation of cortical neurons with neurotrophin-3 (NT-3) also led to a decrease in calretinin expression. However, in contrast to BDNF and N T-4, NT-3 did not affect calbindin expression. Double-labeling experiments evidenced that calretinin- and calbindin-containing neurons belong to disti nct neuronal subpopulations, suggesting that BDNF and NT-4 exert opposite e ffects according to the neurochemical phenotype of the target cell.