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.
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.
Strelau
J
J
Neuroanatomy and Interdisciplinary Center for Neurosciences (IZN), University of Heidelberg, Germany.
Schober
A
A
Sullivan
A
A
Schilling
L
L
Unsicker
K
K
D018663:Adrenergic Agents / Q000009:adverse effects; D000818:Animals; D016923:Cell Death; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002490:Central Nervous System / Q000737:chemistry; D002540:Cerebral Cortex / Q000473:pathology; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D055436:Growth Differentiation Factor 15; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism; D016627:Oxidopamine / Q000009:adverse effects; D011903:Raphe Nuclei / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism*; D014018:Tissue Distribution; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018663:Adrenergic Agents; D016207:Cytokines; C526141:Gdf15 protein, mouse; C526142:Gdf15 protein, rat; D055436:Growth Differentiation Factor 15; D018696:Neuroprotective Agents; D016212:Transforming Growth Factor beta; D016627:Oxidopamine; D004298:Dopamine