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 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.
Leng
Andreas
A
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, CH-8603 Schwerzenbach, Switzerland.
Mura
Anna
A
Feldon
Joram
J
Ferger
Boris
B
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002908:Chronic Disease; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology; D019610:Cytoprotection / Q000235:genetics*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism / Q000503:physiopathology; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; C493215:Slc6a3 protein, mouse; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C069521:recombinant human tumor necrosis factor-binding protein-1; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine