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

Bone morphogenetic proteins (BMPs) are a family of growth differentiation f actors which induce bone formation from mesenchymal cells. These proteins a re members of the transforming growth factor-beta superfamily. The expressi on of BMPs in the nervous system as well as in other tissues has been repor ted. In this study, we show that the presence of BMP-2 resulted in a dose-d ependent increase in the number of tyrosine hydroxylase-immunoreactive vent ral mesencephalic cells after 7 days in serum-free medium cultures. A maxim al response was elicited at 10 ng/mL. BMP-2 also increased the number of pr imary neurites and branch points as well as the length of the longest neuri te in a dose-dependent manner, with a maximal effect at 1 ng/mL, In contras t, 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 pres ence of a high BMP-2 concentration (100 ng/mL), but not with lower doses, s uggesting that the neurotrophic effect in dopaminergic neurons is not media ted by astroglial cells. This is consistent with the fact that the BMP-2 ef fect on dopaminergic neurons was observed even when the cultures were treat ed with alpha-aminoadipic acid to exclude the presence of glial cells. In s ummary, our data indicate that BMP-2 is a potent neurotrophic factor for ve ntral mesencephalic dopaminergic cells in culture, (C) 1999 John Wiley & So ns, Inc.