Bone morphogenetic proteins but not growth differentiation factors induce dopaminergic differentiation in mesencephalic precursors

Abstract

Bone morphogenetic proteins (BMPs) and growth differentiation factors (GDFs) are potential therapeutic molecules for the treatment of Parkinson's disease (PO). Here we compare the effects of BMP3, 5, 6, and 7 and GDF5 and 6 in a rat mesencephalic cell culture system that reflects the developmental stage of neurons around birth. High concentrations of BMP5, 6, and 7 and GDF5 and 6 induced astroglial cell fate and a depletion of oligodendrocytes. Only BMP5, 6, and 7, however, significantly increased the number of tyrosine hydroxylase (TH)-positive neurons and induced nuclear translocation of the phosphorylated BMP-restricted Smad in a substantial number of TH- and microtubule-associated protein 2(MAP2ab)-positive cells. None of the proteins protected TH-positive cells against 6-hydroxydopamine-induced oxidative stress. BMP3 was without any effect throughout the studies. We conclude that BMP5, 6, and 7 act directly and independently on precursors of the dopaminergic and astroglial lineage and induce their differentiation. In contrast, GDF5 and 6 primarily affect nonneuronal cells in mesencephalic cultures of this stage.