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Feeding-produced subchronic high plasma levels of uric acid improve behavioral dysfunction in 6-hydroxydopamine-induced mouse model of Parkinson’s disease

Nakashima, Akioa; Yamauchi, Atsushia; Matsumoto, Junichia; Dohgu, Shinyaa; Takata, Fuyukoa; Koga, Mitsuhisaa; Fukae, Jirob; Tsuboi, Yoshiob; Kataoka, Yasufumia

doi: 10.1097/FBP.0000000000000413
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The development of Parkinson’s disease (PD) involves the degeneration of dopaminergic neurons caused by oxidative stress. Accumulating clinical evidence indicates that high blood levels of uric acid (UA), an intrinsic antioxidative substance, are associated with reduced risk of PD. However, this hypothesis has not been confirmed by in-vivo experiments. The present study investigated the effects of UA on behavioral abnormalities in the development of PD. We used unilateral 6-hydroxydopamine-lesioned mice, which were fed on a diet containing 1% UA and 2.5% potassium oxonate (an uricase inhibitor) to induce hyperuricemia. A significant elevation in UA levels was found in groups that were fed a UA diet. The 6-hydroxydopamine-lesioned mice showed impaired rotarod performance and increased apomorphine-induced contralateral rotations. These behavioral abnormalities were significantly reversed by feeding a UA diet for 1 week before and 5 weeks after surgery (subchronic hyperuricemia). These behavioral improvements occurred in parallel with recovery of tyrosine hydroxylase protein levels in the lesioned striatal side. The present study with a dietary hyperuricemia mice model confirms that UA exerts a neuroprotective effect on dopaminergic neuronal loss, improving motor dysfunction and ameliorating PD development.

aDepartment of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University

bDepartment of Neurology, Fukuoka University School of Medicine, Fukuoka, Japan

Correspondence to Yasufumi Kataoka, PhD, Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan E-mail: ykataoka@fukuoka-u.ac.jp

Received November 29, 2017

Accepted April 20, 2018

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