The neurotoxicity of dopamine (DA) quinones that appears in dopaminergic neuron-specific oxidative stress has recently been shown to play a role in the pathogenesis and/or progression of Parkinson disease. To clarify the effects of a DA agonist, pergolide, on the levodopa-induced elevation of quinones, the authors examined striatal changes in quinoprotein using a hemi-parkinsonian mouse model. The level of striatal quinoprotein was significantly elevated specifically on the parkinsonian side, but not on the control side, after repeated levodopa administration. This levodopa-induced increase in striatal quinoprotein was almost completely suppressed by adjunctive administration with pergolide on the lesioned side. Furthermore, it was clarified that pergolide scavenged DA-semiquinones generated in vitro in a dose-dependent manner. These suppressive and quenching effects of pergolide against cytotoxic DA quinones may play a key role in its neuroprotective mechanism in the parkinsonian brain.
From the Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.
Reprints: Masato Asanuma, MD, PhD, Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama 700-8558, Japan (e-mail: email@example.com).
Supported in part by Grants-in-Aid for Young Scientists and for Scientific Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology, and by Health and Labour Sciences Research Grants for Research on Psychiatric and Neurological Diseases and Mental Health, for Comprehensive Research on Aging and Health, and for Research on Measures for Intractable Diseases from the Japanese Ministry of Health, Labour and Welfare.