TY - JOUR
T1 - Tumor necrosis factor-alpha receptor ablation in a chronic MPTP mouse model of Parkinson's disease
AU - Leng, Andreas
AU - Mura, Anna
AU - Feldon, Joram
AU - Ferger, Boris
N1 - Funding Information:
This work was supported by a grant from the Swiss National Foundation. We thank Ms. E. Weber for genotyping of the genetically modified mice and Mr. Alan Ipekian and Ms. Misa Kuper-Yamanaka for linguistic revision of the manuscript.
PY - 2005/2/28
Y1 - 2005/2/28
N2 - 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 TNF-alpha receptor 1 (-/-) (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 significantly; 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.
AB - 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 TNF-alpha receptor 1 (-/-) (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 significantly; 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.
KW - Cytokine
KW - Inflammation
KW - MPTP
KW - Parkinson's disease
KW - TNF-alpha
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=12744265234&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2004.10.077
DO - 10.1016/j.neulet.2004.10.077
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AN - SCOPUS:12744265234
SN - 0304-3940
VL - 375
SP - 107
EP - 111
JO - Neuroscience Letters
JF - Neuroscience Letters
IS - 2
ER -