Brain-derived neurotrophic factor (BDNF) mediates bone morphogenetic protein-2 (BMP-2) effects on cultured striatal neurones

Bone morphogenetic proteins are members of the transforming growth factor-b eta superfamily that have multiple functions in the developing nervous syst em. One of them, bone morphogenetic protein-2 (BMP-2), promotes the differe ntiation of cultured striatal neurones, enhancing dendrite growth and calbi ndin-positive phenotype. Bone morphogenetic proteins have been implicated i n cooperative interactions with other neurotrophic factors. Here we examine d whether the effects of BMP-2 on cultured striatal neurones are mediated o r enhanced by other neurotrophic factors. BMP-2 had a cooperative effect wi th low doses of brain-derived neurotrophic factor or neurotrophin-3 (but no t with other neurotrophic factors such as glial cell line-derived neurotrop hic factor, neurturin or transforming growth factor-beta2) on the number of calbindin-positive striatal neurones. Moreover, BMP-2 induced phosphorylat ed Trk immunoreactivity in cultured striatal neurones, suggesting that neur otrophins are involved in BMP-2 neurotrophic effects. The addition of TrkB- IgG or antibodies against brain-derived neurotrophic factor abolished the e ffects of BMP-2 on the number and degree of differentiation of calbindin-po sitive striatal neurones. Indeed, BMP-2 treatment increased brain-derived n eurotrophic factor protein levels in treated cultures media and BDNF immuno cytochemistry revealed that this neurotrophin was produced by neuronal cell s. Taken together, these results indicate that brain-derived neurotrophic f actor mediates the effects of BMP-2 on striatal neurones.