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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
Cell and tissue research 2016 v.365 no.2 pp. 209-223
Parkinson disease, animal models, brain, cytokines, dopamine, gene expression regulation, genotype, mice, neurons, transforming growth factor beta
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.