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Abstract Background Parkinson's disease (PD) is a neurodegenerative disorder caused by dopamine neuronal dysfunction. Although dopamine agonists and N-methyl-D-aspartate (NMDA) receptor antagonists are used to treat PD, chronic use causes severe side effects. Therefore, puerarin (PUE) affects the dopamine system and is a considerable candidate for PD; however, its therapeutic effects on PD-associated motor dysfunction remain unclear. Therefore, this study aimed to investigate the effects of PUE treatment on motor dysfunction in a 6-hydroxydopamine (6-OHDA) rodent PD model. Methods Adult male ICR mice received unilateral 6-OHDA microinfusion into the right medial forebrain bundle. After a 2-week recovery period, PUE (20 or 50 mg/kg) or the vehicle (saline, VEH) was intraperitoneally administered once daily for 3 weeks. Motor dysfunction was assessed using the locomotion, rotation, and gait cycle tests 2 weeks after PUE administration. Local field potential (LFP) was measured in the substantia nigra compacta (SNc), striatum (STR), subthalamic nucleus (STN), and primary motor cortex (M1). Results PD animals showed higher unidirectional rotation and abnormal gait cycle without locomotion change compared with sham surgery (control, CTR) animals. PUE treatment ameliorated the abnormal gait cycle of PD animals. These effects were different with DA agonist and NMDA receptor antagonist treatments. Moreover, PUE treatment induced no changes in attenuated LFPs of beta wave in the STR, STN, and M1, and coherence of delta wave between SNc-STN was shown in PD animals. Conclusions This study suggests that PUE is a beneficial co-therapeutic agent for alleviating gait disturbances via dopaminergic and non-dopaminergic neurocircuitry in PD.
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