Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice.
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.
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany.|Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104, Freiburg, Germany.|Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany.
Venissa
V
Machado
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104, Freiburg, Germany.
Ralf
R
Gilsbach
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany.|German Center for Neurodegenerative Diseases, 53115, Bonn, Germany.
Richa
R
Das
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany.
Andreas
A
Schober
Institute of Medical Biometry and Medical Informatics, University of Freiburg, 79104, Freiburg, Germany.
Lioudmila
L
Bogatyreva
German Center for Neurodegenerative Diseases, 53115, Bonn, Germany.
Dieter
D
Hauschke
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany.
Kerstin
K
Krieglstein
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany. ku39@anat.uni-freiburg.de.
Klaus
K
Unsicker
Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany. bjoern.spittau@anat.uni-freiburg.de.
Björn
B
Spittau
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000008:administration & dosage; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000378:metabolism*; D055436:Growth Differentiation Factor 15 / Q000172:deficiency* / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D017072:Neostriatum / Q000378:metabolism* / Q000473:pathology*; D009457:Neuroglia / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism* / Q000473:pathology*
D015415:Biomarkers; D016207:Cytokines; C526141:Gdf15 protein, mouse; D055436:Growth Differentiation Factor 15; D018836:Inflammation Mediators; D012333:RNA, Messenger; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
DAergic neurons; Gdf-15; MPTP; Microglia; Parkinson’s disease