%0 Journal Article
%A Machado, Venissa
%A Gilsbach, Ralf
%A Das, Richa
%A Schober, Andreas
%A Bogatyreva, Lioudmila
%A Hauschke, Dieter
%A Krieglstein, Kerstin
%A Unsicker, Klaus
%A Spittau, Björn
%T Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.
%J Cell & tissue research
%V 365
%N 2
%@ 0302-766X
%C Heidelberg
%I Springer
%M DZNE-2020-04986
%P 209-223
%D 2016
%X 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.
%K 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: administration & dosage
%K Animals
%K Biomarkers: metabolism
%K Cell Proliferation
%K Cytokines: metabolism
%K Dopaminergic Neurons: metabolism
%K Growth Differentiation Factor 15: deficiency
%K Growth Differentiation Factor 15: metabolism
%K Inflammation Mediators: metabolism
%K Mice
%K Neostriatum: metabolism
%K Neostriatum: pathology
%K Neuroglia: metabolism
%K RNA, Messenger: genetics
%K RNA, Messenger: metabolism
%K Substantia Nigra: metabolism
%K Substantia Nigra: pathology
%K Biomarkers (NLM Chemicals)
%K Cytokines (NLM Chemicals)
%K Gdf15 protein, mouse (NLM Chemicals)
%K Growth Differentiation Factor 15 (NLM Chemicals)
%K Inflammation Mediators (NLM Chemicals)
%K RNA, Messenger (NLM Chemicals)
%K 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:27115420
%R 10.1007/s00441-016-2406-x
%U https://pub.dzne.de/record/138664