Growth/differentiation factor-15 (GDF-15), a novel member of the TGF-beta superfamily, promotes survival of lesioned mesencephalic dopaminergic neurons in vitro and in vivo and is induced in neurons following cortical lesioning

J Neural Transm Suppl. 2003:(65):197-203. doi: 10.1007/978-3-7091-0643-3_12.

Abstract

This review summarizes the evidence that GDF-15, a recently discovered member of the TGF-beta superfamily, is a trophic factor for nigral dopamine neurons, both in vitro and in vivo. Specifically, GDF-15 promotes survival and differentiation of embryonic rat dopaminergic neurons, but not of other neuron populations, with the exception of serotonergic raphe neurons. The neurotrophic effect of GDF-15 seems to be direct and not mediated through glial cells. In the rat 6-hydroxydopamine model of parkinsonism GDF-15 rescues intoxicated dopaminergic neurons and abolishes abnormal turning behavior. The most prominent site of synthesis of GDF-15 within the brain is the choroid plexus, which secretes GDF-15 into the cerebrospinal fluid, from where the molecule can penetrate through the ependymal layer into the parenchyma. Analysis of mouse mutants lacking GDF-15 will reveal whether the endogenous factor also has a role in promoting embryonic and protecting lesioned nigral dopamine neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Agents / adverse effects
  • Animals
  • Cell Death
  • Cell Differentiation / drug effects
  • Cell Survival / drug effects
  • Central Nervous System / chemistry
  • Cerebral Cortex / pathology
  • Cytokines / analysis
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Dopamine / metabolism
  • Growth Differentiation Factor 15
  • Mesencephalon / drug effects
  • Mesencephalon / metabolism
  • Neuroglia / metabolism
  • Neurons / drug effects*
  • Neurons / metabolism*
  • Neuroprotective Agents / metabolism
  • Oxidopamine / adverse effects
  • Raphe Nuclei / drug effects
  • Substantia Nigra / drug effects*
  • Substantia Nigra / metabolism*
  • Tissue Distribution
  • Transforming Growth Factor beta / metabolism

Substances

  • Adrenergic Agents
  • Cytokines
  • Gdf15 protein, mouse
  • Gdf15 protein, rat
  • Growth Differentiation Factor 15
  • Neuroprotective Agents
  • Transforming Growth Factor beta
  • Oxidopamine
  • Dopamine