17 Machado, Venissa Gilsbach, Ralf Das, Richa Schober, Andreas Bogatyreva, Lioudmila Hauschke, Dieter Krieglstein, Kerstin Unsicker, Klaus Spittau, Björn Pre 2020 AG Brömer 1 Bonn common Cell & tissue research Cell & tissue research Springer Heidelberg 0302-766X 10.1007/s00441-016-2406-x English 209-223 2 365 Growth/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. PUB:(DE-HGF)16, ; 0, ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: administration & dosage Animals Biomarkers: metabolism Cell Proliferation Cytokines: metabolism Dopaminergic Neurons: metabolism Growth Differentiation Factor 15: deficiency Growth Differentiation Factor 15: metabolism Inflammation Mediators: metabolism Mice Neostriatum: metabolism Neostriatum: pathology Neuroglia: metabolism RNA, Messenger: genetics RNA, Messenger: metabolism Substantia Nigra: metabolism Substantia Nigra: pathology Biomarkers Cytokines Gdf15 protein, mouse Growth Differentiation Factor 15 Inflammation Mediators RNA, Messenger 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Journal Article 2016 DZNE-2020-04986 2016 pmid:27115420 https://pub.dzne.de/record/138664 https://doi.org/10.1007/s00441-016-2406-x