Electroacupuncture Produces the Sustained Motor Improvement in 6-Hydroxydopamine-Lesioned Mice.

Yan Yu,Ke Wang,Jiahui Deng,Jun Jia,Min Sun,Xiaomin Wang,Huaibin Cai

doi:10.1371/journal.pone.0149111

Abstract

Clinical and research evidence has shown that electroacupuncture (EA) promotes recovery of motor function in patients with Parkinson’s disease (PD). However, the “efficacy span” of EA treatment, especially the long-term effect of EA that is thought to last after the cessation of EA treatment, has not been investigated. The present study thus investigated and compared the effect of EA during and after chronic EA application on motor activity and dopamine lesions in a 6-hydroxydopamine (6-OHDA)-lesioned mouse model of PD. Chronic EA treatment (30 min a day, 6 days a week for 2 or 4 weeks) significantly attenuated motor deficiency and reduced dopamine neuron degeneration. Remarkably, EA showed a long-lasting effect after the cessation of EA stimulation. At 2 and 4 weeks after the termination of EA, EA continued to improve motor function in 6-OHDA-lesioned mice. Consistent with sustained behavioral effects, EA induced an enduring increase in the dopamine turnover ratio in the striatum 2 weeks after the cessation of EA treatment. Here we demonstrated that the therapeutic effect of EA outlasted the duration of EA application. During a relatively long period of time after the completion of EA treatment, EA is able to continue to improve motor function and enhance dopamine availability in 6-OHDA-lesioned PD mice.

Highlights

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the elderly
We found that 100 Hz EA significantly increased the latency in the rotarod test at both 2 (Fig 2A) and 4 (Fig 3A) weeks, while 0 Hz EA did not, but 100 Hz EA increased the percentage of contralateral forelimb placement at 2 weeks (39.5 ± 3.8% vs. 21.3 ± 3.7%, P < 0.05, Fig 2B) and 4 (43.7 ± 3.7% vs. 25.8 ± 5.4%, P < 0.05, Fig 3B) weeks after the start of EA stimulation
Similar to the results observed at 2 weeks after the cessation of EA stimulation, EA had no effect on the reduced levels of DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum at 4 weeks after the cessation of EA (Fig 5G–5I). At this time point, EA did not alter dopamine turnover ratios as measured by ratios of DOPAC/DA (Fig 5J), HVA/DA (Fig 5K), and (DOPAC + HVA)/DA (Fig 5L). These results indicate that EA increases the dopamine turnover ratio at the early stage of EA absence (2 weeks), which may be related at least in part to the therapeutic effect of EA seen at this stage

Summary

Introduction

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases in the elderly It mainly affects the motor system and at a late stage it causes other psychiatric symptoms. Our previous studies have demonstrated that high-frequency EA (100 Hz) stimulation significantly reduced abnormal behaviors and enhanced recovery of the dopaminergic nigrostriatal system in rodent’s PD models, including medial forebrain bundle (MFB) axotomy in rats [9], 6-hydroxydopamine (6-OHDA)-induced lesion of MFBs in rats [10], and MPTP-induced dopamine depletion in mice [11]. While the therapeutic effect of EA has been well demonstrated, all early studies have been focused on the effect of EA that was produced during the period of EA stimulation or shortly after EA stimulation This leaves an important question unanswered, i.e., whether the EA effect can sustain after the cessation of EA stimulation.

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