Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice

Machado, Venissa; Gilsbach, Ralf; Das, Richa; Schober, Andreas; Bogatyreva, Lioudmila; Hauschke, Dieter; Krieglstein, Kerstin; Unsicker, Klaus; Spittau, Björn

doi:10.1007/s00441-016-2406-x

Regular Article
Published: 26 April 2016

Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice

Venissa Machado^1,2,3,
Ralf Gilsbach⁴,
Richa Das¹^nAff5,
Andreas Schober¹,
Lioudmila Bogatyreva⁶,
Dieter Hauschke⁵,
Kerstin Krieglstein¹,
Klaus Unsicker¹ &
Björn Spittau¹

Cell and Tissue Research volume 365, pages 209–223 (2016)Cite this article

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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.

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Acknowledgments

We are grateful to Günter Frank for excellent technical assistance.

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Richa Das
Present address: German Center for Neurodegenerative Diseases, 53115, Bonn, Germany

Affiliations

Institute of Anatomy and Cell Biology, Department of Molecular Embryology, University of Freiburg, 79104, Freiburg, Germany
Venissa Machado, Richa Das, Andreas Schober, Kerstin Krieglstein, Klaus Unsicker & Björn Spittau
Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79104, Freiburg, Germany
Venissa Machado
Faculty of Biology, University of Freiburg, 79104, Freiburg, Germany
Venissa Machado
Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104, Freiburg, Germany
Ralf Gilsbach
German Center for Neurodegenerative Diseases, 53115, Bonn, Germany
Dieter Hauschke
Institute of Medical Biometry and Medical Informatics, University of Freiburg, 79104, Freiburg, Germany
Lioudmila Bogatyreva

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Venissa Machado
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Ralf Gilsbach
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Richa Das
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Andreas Schober
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Lioudmila Bogatyreva
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Dieter Hauschke
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Kerstin Krieglstein
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Klaus Unsicker
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Björn Spittau
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Correspondence to Klaus Unsicker or Björn Spittau.

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This study was supported in part by the Excellence Initiative of the German Research Foundation (GSC-4, Spemann Graduate School) and by grants from the German Research Foundation (DFG).

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Machado, V., Gilsbach, R., Das, R. et al. Gdf-15 deficiency does not alter vulnerability of nigrostriatal dopaminergic system in MPTP-intoxicated mice. Cell Tissue Res 365, 209–223 (2016). https://doi.org/10.1007/s00441-016-2406-x

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Received: 11 January 2016
Accepted: 06 April 2016
Published: 26 April 2016
Issue Date: August 2016
DOI: https://doi.org/10.1007/s00441-016-2406-x

Keywords

Gdf-15
MPTP
DAergic neurons
Microglia
Parkinson’s disease