Neuron
Volume 13, Issue 5, November 1994, Pages 1245-1252
Journal home page for Neuron

Article
TGFβ2 and TGFβ3 are potent survival factors for midbrain dopaminergic neurons

https://doi.org/10.1016/0896-6273(94)90062-0Get rights and content

Abstract

The vertebrate ventral midbrain contains 3–4 × 10° dopaminergic neurons that influence motor activity, emotional behavior, and cognition. Recently, glial cell line-derived neurotrophic factor (GDNF) was shown to be a potent survival factor for these dopaminergic neurons in culture. However, many midbrain dopaminergic neurons project to targets that do not express GDNF. We report here that transforming growth factors (TGFs) TGFβ2 and TGFβ3, which are distantly related to GDNF, also prevent the death of cultured rat embryonic midbrain dopaminergic neurons at picomolar concentrations. Furthermore, we find that TGFβ2, TGFβ3, and GDNF are expressed sequentially as local and target-derived trophic factors and that subpopulations of dopaminergic neurons projecting to distinct targets have access to only one of these factors. These findings are consistent with the idea that GDNF, TGFβ2, and TGFβ3 are physiological survival factors for developing midbrain dopaminergic neurons and may have applications as therapeutics for Parkinson's disease, a neurodegenerative disorder of dopaminergic neurons.

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      Transforming growth factor-β (TGF-β) is widely recognized as a critical regulator of key events in development, disease, and repair (Dunker and Krieglstein, 2000; Massague, 1998). TGF-β regulates inflammatory responses after injury in the peripheral and central nervous system (CNS) (Wyss-Coray et al., 1997), and functions as a survival factor for embryonic motoneurons, dopaminergic and neonatal sensory neurons in vitro (Chalazonitis et al., 1992; Krieglstein et al., 1995; Martinou et al., 1990; Poulsen et al., 1994). TGF-β exerts neurotrophic effects on damaged neurons (Prehn et al., 1993), rescues sympathetic neurons from death after destruction of the target cells (Blottner et al., 1996), and protects dopaminergic neurons from N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity and cortical neurons from sodium cyanide or glutamate (Farkas et al., 2003; Krieglstein et al., 1995; Prehn et al., 1993).

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    The last two authors contributed equally to this work.

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