DNA array analysis of the developing rat cerebellum: transforming growth factor-β2 inhibits constitutively activated NF-κB in granule neurons

The nuclear factor-kB (NF-kB) pathway is important in neuronal survival and in integration of external signals e.g. cytokines, glutamate, Ab and nerve growth factor (NGF). During rat cerebellar development NF-kB activity is high in granule cells before postnatal day 7 (P7) and declines after P7. Using gene expression pro®les, measured by cDNA arrays, up-regulation of transforming growth factor-beta2 (TGF-b2) was correlated with the developmental down-regulation of NF-kB. TGF-b2 depicted strongest, more than 4-fold, up-regulation in P12 versus P4 cerebella. In situ hybridization and immunohistochemistry con®ned upregulated TGF-b2 to granule cells and correlated mRNA and TGFb2-protein increase. Finally TGF-b2 repressed NF-kB activity, in an in vitro system resembling migrating cerebellar granule cells. Thus, TGF-b might ful®ll an important role in repressing developmentally activated NF-kB in granule neurons. q 2001 Elsevier Science Ireland Ltd. All rights reserved.