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PMID: 7882977 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

TGF-beta superfamily members promote survival of midbrain dopaminergic neurons and protect them against MPP+ toxicity.

The EMBO journal ·Vol. 14 ·No. 4 ·1995-02-15 ·Pages 736-42

Krieglstein K, Suter-Crazzolara C, Fischer WH, Unsicker K

Abstract

The superfamily of transforming growth factors-beta (TGF-beta) comprises an expanding list of multifunctional proteins serving as regulators of cell proliferation and differentiation. Prominent members of this family include the TGF-beta s 1-5, activins, bone morphogenetic proteins and a recently discovered glial cell line-derived neurotrophic factor (GDNF). In the present study we demonstrate and compare the survival promoting and neuroprotective effects of TGF-beta 1, -2 and -3, activin A and GDNF for midbrain dopaminergic neurons in vitro. All proteins increase the survival of tyrosine hydroxylase-immunoreactive dopaminergic neurons isolated from the embryonic day (E) 14 rat mesencephalon floor to varying extents (TGF-beta s 2.5-fold, activin A and GDNF 1.6-fold). TGF-beta s, activin A and GDNF did not augment numbers of very rarely observed astroglial cells visualized by using antibodies to glial fibrillary acidic protein and had no effect on cell proliferation monitored by incorporation of BrdU. TGF-beta 1 and activin A protected dopaminergic neurons against N-methyl-4-phenylpiridinium ion toxicity. Reverse transcription-polymerase chain reaction (RT-PCR) analysis indicated that TGF-beta 2 mRNA, but not GDNF mRNA, is expressed in the E14 rat midbrain floor and in mesencephalic cultures. We conclude that TGF-beta s 1-3, activin A and GDNF share a neurotrophic capacity for developing dopaminergic neurons, which is not mediated by astroglial cells and not accompanied by an increase in cell proliferation.

Related Genes
FGF-2 GDNF TGF-&bgr 2
MeSH Terms
1-Methyl-4-phenylpyridinium/toxicity Activins Animals Base Sequence Cells, Cultured DNA Primers/chemistry Gene Expression Glial Cell Line-Derived Neurotrophic Factor In Vitro Techniques Inhibins/pharmacology Mesencephalon/cytology,embryology Molecular Sequence Data Nerve Growth Factors Nerve Tissue Proteins/pharmacology RNA, Messenger/genetics Rats Receptors, Dopamine/drug effects Transforming Growth Factor beta/pharmacology Tyrosine 3-Monooxygenase/genetics
Chemicals
DNA Primers Gdnf protein, rat Glial Cell Line-Derived Neurotrophic Factor Nerve Growth Factors Nerve Tissue Proteins RNA, Messenger Receptors, Dopamine Transforming Growth Factor beta Activins Inhibins Tyrosine 3-Monooxygenase 1-Methyl-4-phenylpyridinium
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Krieglstein K
Department of Anatomy and Cell Biology, University of Heidelberg, Germany.
Suter-Crazzolara C
Fischer W H
Unsicker K
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1995-02-15
Pages
736-42
Language
English
Region
England
NLM ID
8208664
PMCID
PMC398139
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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