Journal Article

DZNE-2020-04986

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.

Machado, V. ; Gilsbach, R. ; Das, R.DZNE* ; Schober, A. ; Bogatyreva, L. ; Hauschke, D.DZNE* ; Krieglstein, K. ; Unsicker, K. (Corresponding author) ; Spittau, B.

2016
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00441-016-2406-x

Abstract: 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.

Keyword(s): 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: administration & dosage (MeSH) ; Animals (MeSH) ; Biomarkers: metabolism (MeSH) ; Cell Proliferation (MeSH) ; Cytokines: metabolism (MeSH) ; Dopaminergic Neurons: metabolism (MeSH) ; Growth Differentiation Factor 15: deficiency (MeSH) ; Growth Differentiation Factor 15: metabolism (MeSH) ; Inflammation Mediators: metabolism (MeSH) ; Mice (MeSH) ; Neostriatum: metabolism (MeSH) ; Neostriatum: pathology (MeSH) ; Neuroglia: metabolism (MeSH) ; RNA, Messenger: genetics (MeSH) ; RNA, Messenger: metabolism (MeSH) ; Substantia Nigra: metabolism (MeSH) ; Substantia Nigra: pathology (MeSH) ; Biomarkers ; Cytokines ; Gdf15 protein, mouse ; Growth Differentiation Factor 15 ; Inflammation Mediators ; RNA, Messenger ; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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Contributing Institute(s):

1. DZNE before 2020 (Pre 2020)
2. Ubiquitin-Mediated Processes in Neurodegenerative Diseases (AG Brömer 1)
3. Bonn common (Bonn common)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2016

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Database coverage:
; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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