Determination of reactive oxygen species associated with the degeneration of dopaminergic neurons during dopamine metabolism.
Oxidative stress is believed to be an important mechanism underlying dopamine-induced neuronal damage. This study provides X-band electron spin resonance (ESR) spectroscopic evidence for reactive oxygen species (ROS) generation during dopamine metabolism. The authors induced excess dopamine metabolism in the mouse striatum by bathing it in tyramine-containing perfusate using microdialysis. The addition of tyramine to the perfusate raised the levels of extracellular dopamine and hydrogen peroxide significantly. The ESR signal from hydroxy-TEMPO decayed during tyramine perfusion and treatment with a monoamine-oxidase inhibitor or radical scavenger suppressed the signal decay. Decreases in the number of tyrosine hydroxylase-immunopositive fibres and in dopamine concentration after tyramine perfusion were observed. Moreover, the tyramine-perfused mice showed a marked methamphetamine-induced rotational response. Notably, these effects of tyramine were suppressed by the simultaneous perfusion of hydroxy-TEMPO. These findings indicate that the ROS generation, which was monitored by hydroxy-TEMPO, caused oxidative damage to the dopaminergic neurons.
Yamato
Mayumi
M
Department of REDOX Medicinal Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. yamato68@redoxnavi.med.kyushu-u.ac.jp
Kudo
Wataru
W
Shiba
Takeshi
T
Yamada
Ken-iichi
KI
Watanabe
Toshiaki
T
Utsumi
Hideo
H
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014439:Tyramine / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; C003959:TEMPO; D004298:Dopamine; D014439:Tyramine