Chronic administration with rotenone does not enhance MPTP neurotoxicity in C57BL/6 mice.
Systematic administration of rotenone as one of pesticides is known to produce degeneration of nigral dopaminergic neurons and motor deficits in experimental animals. Here, we investigated to determine whether systematic administration of rotenone causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Rotenone was injected into MPTP-treated mice over a period of 4 weeks. Thereafter, we evaluated the effect of rotenone 1, 3, and 6 weeks after the cessation of treatment with rotenone. In the present study with HPLC analysis, rotenone did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Furthermore, MPTP + rotenone (9 mg/kg)-treated mice exhibit a significant loss of motor activity 1 day after the cessation of treatment with rotenone, However, no significant change of motor activity was found in MPTP-treated and MPTP + rotenone (9 mg/kg)-treated animals 6 weeks after the cessation of treatment with 0.5% carboxymethyl cellulose or rotenone. Our Western blot analysis study demonstrated that the change of tyrosine hydroxylase and glial fibrillary acidic protein protein levels in MPTP-treated mice was similar than that in MPTP + rotenone-treated animals. These results suggest that rotenone did not enhance MPTP neurotoxicity in mice. Our findings suggest that rotenone is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of PD for exposure to agricultural pesticides.
Aoki
Eriko
E
Department of Neurobiology and Therapeutics, Graduate School and Faculty of Pharmaceutical Sciences, The University of Tokushima, 1-78, Sho-machi, Tokushima, 770-8505, Japan.
Yokoyama
Hironori
H
Kimoto
Hiroki
H
Yano
Ryohei
R
Kato
Hiroyuki
H
Araki
Tsutomu
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009483:Neuropsychological Tests; D012402:Rotenone / Q000378:metabolism / Q000494:pharmacology; D014475:Uncoupling Agents / Q000378:metabolism / Q000494:pharmacology
D015259:Dopamine Agents; D014475:Uncoupling Agents; D012402:Rotenone; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine