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Trophic and protective effects of growth/differentiation factor 5, a member of the transforming growth factor‐β superfamily, on midbrain dopaminergic neurons
Author(s) -
Krieglstein K.,
SuterCrazzolara C.,
Hötten G.,
Pohl J.,
Unsicker K.
Publication year - 1995
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490420516
Subject(s) - dopaminergic , growth differentiation factor , midbrain , transforming growth factor , superfamily , nerve growth factor , neuroscience , growth factor , gdf15 , biology , dopamine , microbiology and biotechnology , endocrinology , genetics , receptor , central nervous system , gene , bone morphogenetic protein
Growth/differentiation factor 5 (GDF5) is a novel member of the transforming growth factor‐β (TGF‐β) superfamily of multifunctional cytokines. We show here that GDF5 is expressed in the developing CNS including the mesencephalon and acts as a neurotrophic, survival promoting molecule for rat dopaminergic midbrain neurons, which degenerate in Parkinson's disease. Recombinant human GDF5 supports dopaminergic neurons, dissected at embryonic day (E) 14 and cultured for 8 days under serum‐free conditions, to almost the same extent as TGF‐β, and is as effective as glial cell line‐derived neurotrophic factor (GDNF), two established trophic factors for midbrain dopaminergic neurons. In contrast to TGF‐β and GDNF, GDF5 augments numbers of astroglial cells in the cultures, suggesting that it may act indirectly and through pathways different from those triggered by TGF‐β and GDNF. GDF5 also protects dopaminergic neurons against the toxicity of N‐methylpyridinium ion (MPP + ), which selectively damages dopaminergic neurons through mechanisms currently debated in the etiology of Parkinson's disease (PD). GDF5 may therefore now be tested in animal models of PD and might become useful in the treatment of PD. © 1995 Wiley‐Liss, Inc.