DNA array analysis of the developing rat cerebellum: transforming growth factor-beta 2 inhibits constitutively activated NF-kappa B in granule neurons

The nuclear factor-kappaB (NF-kappaB) pathway is important in neuronal surv ival and in integration of external signals e.g. cytokines. glutamate, AP a nd nerve growth factor (NGF). During rat cerebellar development NF-kappaB a ctivity is high in granule cells before postnatal day 7 (P7) and declines a fter P7. Using gene expression profiles, measured by cDNA arrays, up-regula tion of transforming growth factor-beta2 (TGF-beta2) was correlated with th e developmental down-regulation of NF-kappaB. TGF-beta2 depicted strongest, more than 4-fold, up-regulation in P12 versus P4 cerebella. In situ hybrid ization and immunohistochemistry confined upregulated TGF-beta2 to granule cells and correlated mRNA and TGF-beta2-protein increase. Finally TGF-beta2 repressed NF-kappaB activity, in an in vitro system resembling migrating c erebellar granule cells. Thus, TGF-beta might fulfill an important role in repressing developmentally activated NF-kappaB in granule neurons. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.