TY  - JOUR
AU  - Machado, Venissa
AU  - Gilsbach, Ralf
AU  - Das, Richa
AU  - Schober, Andreas
AU  - Bogatyreva, Lioudmila
AU  - Hauschke, Dieter
AU  - Krieglstein, Kerstin
AU  - Unsicker, Klaus
AU  - Spittau, Björn
TI  - Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.
JO  - Cell & tissue research
VL  - 365
IS  - 2
SN  - 0302-766X
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2020-04986
SP  - 209-223
PY  - 2016
AB  - 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.
KW  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: administration & dosage
KW  - Animals
KW  - Biomarkers: metabolism
KW  - Cell Proliferation
KW  - Cytokines: metabolism
KW  - Dopaminergic Neurons: metabolism
KW  - Growth Differentiation Factor 15: deficiency
KW  - Growth Differentiation Factor 15: metabolism
KW  - Inflammation Mediators: metabolism
KW  - Mice
KW  - Neostriatum: metabolism
KW  - Neostriatum: pathology
KW  - Neuroglia: metabolism
KW  - RNA, Messenger: genetics
KW  - RNA, Messenger: metabolism
KW  - Substantia Nigra: metabolism
KW  - Substantia Nigra: pathology
KW  - Biomarkers (NLM Chemicals)
KW  - Cytokines (NLM Chemicals)
KW  - Gdf15 protein, mouse (NLM Chemicals)
KW  - Growth Differentiation Factor 15 (NLM Chemicals)
KW  - Inflammation Mediators (NLM Chemicals)
KW  - RNA, Messenger (NLM Chemicals)
KW  - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:27115420
DO  - DOI:10.1007/s00441-016-2406-x
UR  - https://pub.dzne.de/record/138664
ER  -