Transforming growth factor-beta 1 enhances expression of brain-derived neurotrophic factor and its receptor, TrkB, in neurons cultured from rat cerebral cortex

The effects of transforming growth factor (TGF)-beta1 on expression of brai n-derived neurotrophic factor (BDNF) and Its high-affinity receptor, TrkB, in neurons cultured from the cerebral cortex of 18-day-old embryonic rats w ere examined. BDNF mRNA was significantly increased from 24-48 hr after the TGF-beta1 treatment over 20 ng/ml. Accumulation of BDNF protein in the cul ture medium was also potentiated by TGF-beta1, although the intracellular c ontent of BDNF was nearly unchanged. The enhancement of BDNF mRNA expressio n was suppressed by the co-presence of decorin, a small TGF-beta -binding p roteoglycan that inhibits the biological activities of TGF-betas. mRNA expr ession of full-length TrkB, the bioactive high-affinity receptor for BDNF, was also upregulated after treatment with TGF-beta1. These observations sug gest that: 1) TGF-beta1 potentiates BDNF/TrkB autocrine or local paracrine system; and 2) the neurotrophic activity of TGF-beta1 is partly responsible for the BDNF induced by TGF-beta1 itself. To test this latter possibility, we examined the neuronal survival activity of TGF-beta1 with or without K2 52a, a selective inhibitor of Trk family tyrosine kinases. TGF-beta1 signif icantly enhanced neuronal survival, but the co-presence of K252a completely suppressed the activity, demonstrating the involvement of Trk receptor sig naling in TGF-beta1-mediated neuronal survival in cultured rat cortical neu rons. These results seem to be In line with recent findings by other invest igators that some neurotrophic factors including BDNF require TGF-betas as a cofactor to exert their neurotrophic activities. (C) 2001 Wiley-Liss, inc .