Tumor necrosis factor-alpha receptor ablation in a chronic MPTP mouse model of Parkinson's disease

Recently, we demonstrated that mice deficient of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) were partly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity.. Here we extended the study and investigated TNFalpha receptor I (-/-) (TNFR1) and TNF-alpha receptor 2 (-/-) (TNFR2) mice using a chronic MPTP dosing regimen (15 mg/kg MPTP on 8 consecutive days). One week after the last MPTP treatment, HPLC determination of striatal dopamine (DA) and immunostaining for the dopamine transporter (DAT) in the substantia nigra pars compacta (SNpc) was performed. MPTP treatment reduced striatal DA levels sigpificantly; nigral DAT immunoreactivity was reduced to a lower extent. However, there was no difference in DA levels and the number of DAT positive neurons between TNFR1 (-/-), TNFR2 and wild type mice after MPTP treatment. In contrast to TNF-alpha deficiency neither TNFR1 nor TNFR2 gene ablation showed protection against MPTP neurotoxicity, which argues for a protective mechanism of TNF-alpha not mediated by TNFR1 and TNFR2 signaling; (C) 2004 Elsevier Ireland Ltd. All rights reserved.