Abstract

Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. Coenzyme Q10, an antioxidant, has been considered a promising neuroprotective agent; however, conventional oral administration provides limited efficacy due to its very low bioavailability. In this study, we hypothesised that continuous, intrastriatal administration of a low dose of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson’s disease rat model induced by 6-hydroxydopamine was established, and the treatment was applied a week before the full establishment of this disease model. Behavioural tests showed a dramatically decreased number of asymmetric rotations in the intrastriatal Coenzyme Q10 group compared with the no treatment group. Rats with intrastriatal Coenzyme Q10 exposure also exhibited a larger number of dopaminergic neurons, higher expression of neurogenetic and angiogenetic factors, and less inflammation, and the effects were more prominent than those of orally administered Coenzyme Q10, although the dose of intrastriatal Coenzyme Q10 was 17,000-times lower than that of orally-administered Coenzyme Q10. Therefore, continuous, intrastriatal delivery of Coenzyme Q10, especially when combined with implantable devices for convection-enhanced delivery or deep brain stimulation, can be an effective strategy to prevent neurodegeneration in Parkinson’s disease.

Highlights

  • Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression

  • We aimed to investigate the therapeutic efficacy of coenzyme Q10 (CoQ10) delivered locally into the striatum, which was tested in 6-hydroxydopamine (6-OHDA)-induced rat models of Parkinson’s disease

  • An Alzet pump filled with pH 7.4 phosphate-buffered saline (PBS) without CoQ10 was prepared to produce the Alzet-PBS as a control

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Summary

Introduction

Parkinson’s disease is a neurodegenerative disorder, and no treatment has been yet established to prevent disease progression. We hypothesised that continuous, intrastriatal administration of a low dose of Coenzyme Q10 could effectively prevent dopaminergic neuron degeneration. To this end, a Parkinson’s disease rat model induced by 6-hydroxydopamine was established, and the treatment was applied a week before the full establishment of this disease model. Nigral cell death is caused by mitochondrial dysfunction, which is triggered by abnormal energy metabolism and enhanced cellular oxidative stress[9,10] In this regard, there is substantial interest in exploring the use of antioxidants such as coenzyme Q10 (CoQ10) as potential therapies for Parkinson’s disease[11,12]. The progression of nigral cell death was compared with that in animals treated with a larger dose of orally administered CoQ10

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