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

Yu Y, Wang K, Deng J, Sun M, Jia J, Wang X - PLoS ONE (2016)

Bottom Line: 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.Here we demonstrated that the therapeutic effect of EA outlasted the duration of EA application.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neurobiology and Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University, Beijing Institute for Brain Disorders, Beijing, 100069, China.

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.

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Related in: MedlinePlus

Dopamine and its metabolites in the striatum at the 2nd and 4th week after the termination of EA stimulation in 6-OHDA-lesioned mice.Contents of DA(A), DOPAC(B), HVA(C), and turnover ratios of DOPAC/DA (D), HVA/DA (E), (DOPAC plus HVA)/DA (F) in the striatum were analyzed at the end of 2nd week after the termination EA treatment (EA 4 Weeks / 2 Weeks). DA (G), DOPAC (H), HVA (I), DOPAC/DA (J), HVA/DA (K), (DOPAC plus HVA)/DA (L) were analyzed at the end of 4th week after the termination of four-week EA stimulation (EA 4 Weeks / 4 Weeks). The values were expressed as means ± SEM. n = 7 per group. * P <0.05; ** P <0.01; *** P <0.001 vs. Sham group. # P < 0.05; ## P <0.01 vs. 6-OHDA group.
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pone.0149111.g005: Dopamine and its metabolites in the striatum at the 2nd and 4th week after the termination of EA stimulation in 6-OHDA-lesioned mice.Contents of DA(A), DOPAC(B), HVA(C), and turnover ratios of DOPAC/DA (D), HVA/DA (E), (DOPAC plus HVA)/DA (F) in the striatum were analyzed at the end of 2nd week after the termination EA treatment (EA 4 Weeks / 2 Weeks). DA (G), DOPAC (H), HVA (I), DOPAC/DA (J), HVA/DA (K), (DOPAC plus HVA)/DA (L) were analyzed at the end of 4th week after the termination of four-week EA stimulation (EA 4 Weeks / 4 Weeks). The values were expressed as means ± SEM. n = 7 per group. * P <0.05; ** P <0.01; *** P <0.001 vs. Sham group. # P < 0.05; ## P <0.01 vs. 6-OHDA group.

Mentions: Previous studies suggest that EA exerted its improvement of motor dysfunction during its therapeutic stage through enhancing the dopamine metabolism but not restoring dopamine in PD mice [10,21]. To determine whether this is the case for the sustained effect of EA, we measured changes in the content of striatal DA and its metabolites DOPAC and HVA in the lesioned hemisphere with HPLC 2 and 4 weeks after the termination of EA stimulation. As shown in Fig 5, 6-OHDA induced a marked reduction of the concentration of DA (0.172 ± 0.041 μg/mg tissue of 6-OHDA group vs. 0.713 ± 0.030 μg/mg tissue of sham group, P < 0.001, Fig 5A) and its metabolites DOPAC (0.085 ± 0.009 μg/mg tissue of 6-OHDA group vs. 0.257 ± 0.011 μg/mg tissue of sham group, P < 0.001, Fig 5B) and HVA (0.042 ± 0.002 μg/mg tissue of 6-OHDA group vs. 0.086 ± 0.005 μg/mg tissue of sham group, P<0.001, Fig 5C). 100 Hz EA had no influence on levels of DA, DOPAC and HVA at 2 weeks after the completion of 4-week EA treatment. However, EA at 100 Hz significantly increased dopamine turnover ratios as detected by the DOPAC/DA ratio (0.950 ± 0.118 of EA group vs. 0.567 ± 0.036 of sham group, P < 0.01, Fig 5D), the HVA/DA ratio (0.375 ± 0.043 of EA group vs. 0.247 ± 0.021 of sham group, P < 0.01, Fig 5E), and the (DOPAC + HVA)/DA ratio (1.227 ± 0.158 of EA group vs. 0.814 ± 0.105 of sham group, P < 0.05, Fig 5F). Similar to the results observed at 2 weeks after the cessation of EA stimulation, EA had no effect on the reduced levels of DA, DOPAC and HVA in the striatum at 4 weeks after the cessation of EA (Fig 5G–5I). However, 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.


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

Yu Y, Wang K, Deng J, Sun M, Jia J, Wang X - PLoS ONE (2016)

Dopamine and its metabolites in the striatum at the 2nd and 4th week after the termination of EA stimulation in 6-OHDA-lesioned mice.Contents of DA(A), DOPAC(B), HVA(C), and turnover ratios of DOPAC/DA (D), HVA/DA (E), (DOPAC plus HVA)/DA (F) in the striatum were analyzed at the end of 2nd week after the termination EA treatment (EA 4 Weeks / 2 Weeks). DA (G), DOPAC (H), HVA (I), DOPAC/DA (J), HVA/DA (K), (DOPAC plus HVA)/DA (L) were analyzed at the end of 4th week after the termination of four-week EA stimulation (EA 4 Weeks / 4 Weeks). The values were expressed as means ± SEM. n = 7 per group. * P <0.05; ** P <0.01; *** P <0.001 vs. Sham group. # P < 0.05; ## P <0.01 vs. 6-OHDA group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4764645&req=5

pone.0149111.g005: Dopamine and its metabolites in the striatum at the 2nd and 4th week after the termination of EA stimulation in 6-OHDA-lesioned mice.Contents of DA(A), DOPAC(B), HVA(C), and turnover ratios of DOPAC/DA (D), HVA/DA (E), (DOPAC plus HVA)/DA (F) in the striatum were analyzed at the end of 2nd week after the termination EA treatment (EA 4 Weeks / 2 Weeks). DA (G), DOPAC (H), HVA (I), DOPAC/DA (J), HVA/DA (K), (DOPAC plus HVA)/DA (L) were analyzed at the end of 4th week after the termination of four-week EA stimulation (EA 4 Weeks / 4 Weeks). The values were expressed as means ± SEM. n = 7 per group. * P <0.05; ** P <0.01; *** P <0.001 vs. Sham group. # P < 0.05; ## P <0.01 vs. 6-OHDA group.
Mentions: Previous studies suggest that EA exerted its improvement of motor dysfunction during its therapeutic stage through enhancing the dopamine metabolism but not restoring dopamine in PD mice [10,21]. To determine whether this is the case for the sustained effect of EA, we measured changes in the content of striatal DA and its metabolites DOPAC and HVA in the lesioned hemisphere with HPLC 2 and 4 weeks after the termination of EA stimulation. As shown in Fig 5, 6-OHDA induced a marked reduction of the concentration of DA (0.172 ± 0.041 μg/mg tissue of 6-OHDA group vs. 0.713 ± 0.030 μg/mg tissue of sham group, P < 0.001, Fig 5A) and its metabolites DOPAC (0.085 ± 0.009 μg/mg tissue of 6-OHDA group vs. 0.257 ± 0.011 μg/mg tissue of sham group, P < 0.001, Fig 5B) and HVA (0.042 ± 0.002 μg/mg tissue of 6-OHDA group vs. 0.086 ± 0.005 μg/mg tissue of sham group, P<0.001, Fig 5C). 100 Hz EA had no influence on levels of DA, DOPAC and HVA at 2 weeks after the completion of 4-week EA treatment. However, EA at 100 Hz significantly increased dopamine turnover ratios as detected by the DOPAC/DA ratio (0.950 ± 0.118 of EA group vs. 0.567 ± 0.036 of sham group, P < 0.01, Fig 5D), the HVA/DA ratio (0.375 ± 0.043 of EA group vs. 0.247 ± 0.021 of sham group, P < 0.01, Fig 5E), and the (DOPAC + HVA)/DA ratio (1.227 ± 0.158 of EA group vs. 0.814 ± 0.105 of sham group, P < 0.05, Fig 5F). Similar to the results observed at 2 weeks after the cessation of EA stimulation, EA had no effect on the reduced levels of DA, DOPAC and HVA in the striatum at 4 weeks after the cessation of EA (Fig 5G–5I). However, 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.

Bottom Line: 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.Here we demonstrated that the therapeutic effect of EA outlasted the duration of EA application.

View Article: PubMed Central - PubMed

Affiliation: Departments of Neurobiology and Physiology, Key Laboratory for Neurodegenerative Disorders of the Ministry of Education, Beijing Key Laboratory for Parkinson's Disease, Capital Medical University, Beijing Institute for Brain Disorders, Beijing, 100069, China.

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.

Show MeSH
Related in: MedlinePlus