TY - JOUR
T1 - Bone morphogenetic proteins but not growth differentiation factors induce dopaminergic differentiation in mesencephalic precursors
AU - Brederlau, Anke
AU - Faigle, R.
AU - Kaplan, P.
AU - Odin, P.
AU - Funa, K.
N1 - Funding Information:
We thank P. S. Eriksson for helpful discussions and for reviewing the manuscript. The work was supported by grants from the Medical Research Council, the Inga and Arne Lundberg Foundation, and the Medical Faculty at Göteborg University. R. Faigle was supported by Adlerbertska Hospitiefonden. A. Brederlau was supported by the Boehringer Ingelheim Foundation.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1006/mcne.2002.1178
DO - 10.1006/mcne.2002.1178
M3 - Article
C2 - 12498780
AN - SCOPUS:0036935247
SN - 1044-7431
VL - 21
SP - 367
EP - 378
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 3
ER -