TGF-beta promotes survival on mesencephalic dopaminergic neurons in cooperation with Shh and FGF-8.
Impaired neuronal survival is a key event in the development of degenerative diseases, such as Parkinson's disease (PD). Here we show that transforming growth factor beta (TGF-beta) acts directly on rat E14 midbrain dopaminergic neurons in vitro, its survival-promoting effect being not mediated by BDNF, NT-3, or GDNF. Treatment with TGF-beta, sonic hedgehog (Shh), or fibroblast growth factor-8 (FGF8) significantly increased number of tyrosine hydroxylase (TH)-immunoreactive neurons after 7 days, whereas application of these factors added together further increased number of TH-positive neurons, compared to single-factor treatments. Neutralization of endogenous TGF-beta, Shh, or FGF8 significantly reduced number of dopaminergic neurons. TGF-beta treatment decreased number of apoptotic cells, having no effect on cell proliferation. Neutralization of TGF-beta in vivo during chick E6-10 resulted in reduced number of midbrain dopaminergic neurons. The results suggest that TGF-beta is required for survival of mesencephalic dopaminergic neurons acting in cooperation with Shh and FGF8.
Roussa
Eleni
E
Department for Neuroanatomy, Center of Anatomy, Georg-August-University Göttingen, 37075 Goettingen, Germany. eroussa@gwdg.de
Farkas
Lilla M
LM
Krieglstein
Kerstin
K
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004298:Dopamine / Q000502:physiology*; D004357:Drug Synergism; D005260:Female; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors / Q000494:pharmacology*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D008024:Ligands; D008636:Mesencephalon / Q000166:cytology; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism; D020812:Receptor, trkC / Q000378:metabolism; D015534:Trans-Activators / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C496458:Fgf8 protein, rat; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D053823:Hedgehog Proteins; D008024:Ligands; D009414:Nerve Growth Factors; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051524:Fibroblast Growth Factor 8; D005346:Fibroblast Growth Factors; D020813:Receptor, trkB; D020812:Receptor, trkC; D004298:Dopamine