engMachado, VenissaGilsbach, RalfDas, RichaSchober, AndreasBogatyreva, LioudmilaHauschke, DieterKrieglstein, KerstinUnsicker, KlausSpittau, BjörnGdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.info:eu-repo/classification/ddc/6101-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: administration & dosageAnimalsBiomarkers: metabolismCell ProliferationCytokines: metabolismDopaminergic Neurons: metabolismGrowth Differentiation Factor 15: deficiencyGrowth Differentiation Factor 15: metabolismInflammation Mediators: metabolismMiceNeostriatum: metabolismNeostriatum: pathologyNeuroglia: metabolismRNA, Messenger: geneticsRNA, Messenger: metabolismSubstantia Nigra: metabolismSubstantia Nigra: pathologyBiomarkersCytokinesGdf15 protein, mouseGrowth Differentiation Factor 15Inflammation MediatorsRNA, Messenger1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridineGrowth/differentiation factor-15 (Gdf-15) is a member of the transforming growth factor-β (Tgf-β) superfamily and has been shown to be a potent neurotrophic factor for midbrain dopaminergic (DAergic) neurons both in vitro and in vivo. Gdf-15 has also been shown to be involved in inflammatory processes. The aim of this study was to identify the role of endogenous Gdf-15 in the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease (PD) by comparing Gdf-15 (+/+) and Gdf-15 (-/-) mice. At 4 days and 14 days post-MPTP administration, both Gdf-15 (+/+) and Gdf-15 (-/-) mice showed a similar decline in DAergic neuron numbers and in striatal dopamine (DA) levels. This was followed by a comparable restorative phase at 90 days and 120 days, indicating that the absence of Gdf-15 does not affect the susceptibility or the recovery capacity of the nigrostriatal system after MPTP administration. The MPTP-induced microglial and astrocytic response was not significantly altered between the two genotypes. However, pro-inflammatory and anti-inflammatory cytokine profiling revealed the differential expression of markers in Gdf-15 (+/+) and Gdf-15 (-/-) mice after MPTP administration. Thus, the MPTP mouse model fails to uncover a major role of endogenous Gdf-15 in the protection of MPTP-lesioned nigrostriatal DAergic neurons, in contrast to its capacity to protect the 6-hydroxydopamine-intoxicated nigrostriatal system.Cell & tissue research 365(2), 209-223 (2016). doi:10.1007/s00441-016-2406-xinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionSpringer2016info:eu-repo/semantics/closedAccessDEhttps://pub.dzne.de/record/138664https://pub.dzne.de/search?p=id:%22DZNE-2020-04986%22Researchersinfo:eu-repo/semantics/altIdentifier/issn/0044-3794info:eu-repo/semantics/altIdentifier/issn/0373-031Xinfo:eu-repo/semantics/altIdentifier/issn/0302-766Xinfo:eu-repo/semantics/altIdentifier/doi/10.1007/s00441-016-2406-xinfo:eu-repo/semantics/altIdentifier/pmid/pmid:27115420info:eu-repo/semantics/altIdentifier/issn/1432-0878info:eu-repo/semantics/altIdentifier/issn/0340-0387info:eu-repo/semantics/altIdentifier/issn/2192-5917info:eu-repo/semantics/altIdentifier/issn/0340-0336