title: 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.
authors.affiliation: Institute of Anatomy and Cell Biology, Göteborg University, SE 40530, Göteborg, Sweden. anke.brederlau@anatcell.gu.se
authors.forename: A
authors.initials: A
authors.lastname: Brederlau
authors.forename: R
authors.initials: R
authors.lastname: Faigle
authors.forename: P
authors.initials: P
authors.lastname: Kaplan
authors.forename: P
authors.initials: P
authors.lastname: Odin
authors.forename: K
authors.initials: K
authors.lastname: Funa
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005333:Fetus; D006085:Graft Survival / Q000187:drug effects* / Q000502:physiology; D006133:Growth Substances / Q000494:pharmacology* / Q000627:therapeutic use; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000494:pharmacology; D010300:Parkinson Disease / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D019485:Bone Morphogenetic Proteins; D006133:Growth Substances; D018696:Neuroprotective Agents; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine