Bone morphogenetic protein-2 promotes dissociated effects on the number and differentiation of cultured ventral mesencephalic dopaminergic neurons

Abstract

Bone morphogenetic proteins (BMPs) are a family of growth differentiation factors which induce bone formation from mesenchymal cells. These proteins are members of the transforming growth factor-beta super-family. The expression of BMPs in the nervous system as well as in other tissues has been reported. In this study, we show that the presence of BMP-2 resulted in a dose-dependent increase in the number of tyrosine hydroxylase-immunoreactive ventral mesencephalic cells after 7 days in serum-free medium cultures. A maximal response was elicited at 10 ng/mL. BMP-2 also increased the number of primary neurites and branch points as well as the length of the longest neurite in a dose-dependent manner, with a maximal effect at 1 ng/mL. In contrast, BMP-2 did not modify the number or the function of GABAergic neurons. On the other hand, we observed stimulation of proliferation and morphological changes in glial cells (astrocytes become more fibrous shaped) in the presence of a high BMP-2 concentration (100 ng/mL), but not with lower doses, suggesting that the neurotrophic effect in dopaminergic neurons is not mediated by astroglial cells. This is consistent with the fact that the BMP-2 effect on dopaminergic neurons was observed even when the cultures were treated with alpha-aminoadipic acid to exclude the presence of glial cells. In summary, our data indicate that BMP-2 is a potent neurotrophic factor for ventral mesencephalic dopaminergic cells in culture.