Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo

• Verfasst von: Strelau, Jens [VerfasserIn]
• Verfasst von: Böttner, Martina [VerfasserIn]
• Verfasst von: Lingor, Paul [VerfasserIn]
• Verfasst von: Suter-Crazzolara, Clemens [VerfasserIn]
• Verfasst von: Galter, Dagmar [VerfasserIn]
• Verfasst von: Jászai, József [VerfasserIn]
• Verfasst von: Krieglstein, Kerstin [VerfasserIn]
• Verfasst von: Unsicker, Klaus [VerfasserIn]
• Titel: Growth/differentiation factor-15/macrophage inhibitory cytokine-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo
• Verf.angabe: Jens Strelau, Aideen Sullivan, Martina Böttner, Paul Lingor, Elisabeth Falkenstein, Clemens Suter-Crazzolara, Dagmar Galter, Jozsef Jaszai, Kerstin Krieglstein, and Klaus Unsicker
• Umfang: 7 S.
• Fussnoten: Gesehen am 20.11.2016 ; Von den Autoren angegeben als: "GDF-15/MIC-1 is a novel trophic factor for midbrain dopaminergic neurons in vivo"
• Titel Quelle: Enthalten in: The journal of neuroscience
• Jahr Quelle: 2000
• Band/Heft Quelle: 20(2000), 23, S. 8597-8603
• ISSN Quelle: 1529-2401
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 155025779X

Abstract

Transforming growth factor-βs (TGF-βs) constitute an expanding family of multifunctional cytokines with prominent roles in development, cell proliferation, differentiation, and repair. We have cloned, expressed, and raised antibodies against a distant member of the TGF-βs, growth/differentiation factor-15 (GDF-15). GDF-15 is identical to macrophage inhibitory cytokine-1 (MIC-1). GDF-15/MIC-1 mRNA and protein are widely distributed in the developing and adult CNS and peripheral nervous systems, including choroid plexus and CSF. GDF-15/MIC-1 is a potent survival promoting and protective factor for cultured and iron-intoxicated dopaminergic (DAergic) neurons cultured from the embryonic rat midbrain floor. The trophic effect of GDF-15/MIC-1 was not accompanied by an increase in cell proliferation and astroglial maturation, suggesting that GDF-15/MIC-1 probably acts directly on neurons. GDF-15/MIC-1 also protects 6-hydroxydopamine (6-OHDA)-lesioned nigrostriatal DAergic neuronsin vivo. Unilateral injections of GDF-15/MIC-1 into the medial forebrain bundle just above the substantia nigra (SN) and into the left ventricle (20 μg each) immediately before a 6-OHDA injection (8 μg) prevented 6-OHDA-induced rotational behavior and significantly reduced losses of DAergic neurons in the SN. This protection was evident for at least 1 month. Administration of 5 μg of GDF-15/MIC-1 in the same paradigm also provided significant neuroprotection. GDF-15/MIC-1 also promoted the serotonergic phenotype of cultured raphe neurons but did not support survival of rat motoneurons. Thus, GDF-15/MIC-1 is a novel neurotrophic factor with prominent effects on DAergic and serotonergic neurons. GDF-15/MIC-1 may therefore have a potential for the treatment of Parkinson's disease and disorders of the serotonergic system.