Increase in level of tumor necrosis factor (TNF)-alpha in 6-hydroxydopamine-lesioned striatum in rats without influence of systemic L-DOPA on the TNF-alpha induction.
We previously reported that the levels of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha are increased in the striatum and cerebrospinal fluid from patients with Parkinson's disease (PD) and in the striatum from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, a murine model of PD. Presently we examined the changes in cytokine levels in the nigrostriatal dopaminergic regions in rats treated with an intrastriatal injection of 6-hydroxydopamine (6-OHDA) as a model of slowly progressive neurodegeneration similar to that seen in PD. We compared the content of TNF-alpha in the nigrostriatal dopaminergic regions of the control side with that of the 6-OHDA-injected experimental side, and also explored the effects of 6-OHDA injection combined with the L-DOPA treatment on the TNF-alpha level in the dopaminergic regions of rats. TNF-alpha was measured by a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA). The concentrations of TNF-alpha in the dopaminergic regions (striatum and substantia nigra) on the 6-OHDA injection side (right side: R) were significantly higher than those in the regions on the control side (left side: L) (Wilcoxon's test, P < 0.05). The ratio of the concentration of TNF-alpha on the injection side to that on the control side (TNF-alpha (R/L)) of each rat was not significantly different in the striatum and substantia nigra between the control group and the group treated with 25 or 50 mg/kg L-DOPA (Mann-Whitney Utests). These results show that TNF-alpha is increased in the striatum and substantia nigra in 6-OHDA-injected dopaminergic regions in rats, which finding is similar to the increase in the striatal dopaminergic regions in patients with PD. The results also indicate that L-DOPA alone or together with 6-OHDA does not increase the level of TNF-alpha in the brain in vivo.
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya, Japan.
M
M
Mogi
A
A
Togari
K
K
Tanaka
N
N
Ogawa
H
H
Ichinose
T
T
Nagatsu
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007980:Levodopa / Q000502:physiology*; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D014409:Tumor Necrosis Factor-alpha; D007980:Levodopa; D016627:Oxidopamine