Xiao-Jun Feng1, Yu-Ting Huang2, Ying-Zu Huang3, Chi-Wei Kuo4, Chih-Wei Peng5, Alexander Rotenberg6, Chi-Hung Juan7, Yu-Cheng Pei8, Yuan-Hao Chen9, Kai-Yun Chen10, Yung-Hsiao Chiang11, Hui-Hua Liu12, Jian-Xian Wu13, Tsung-Hsun Hsieh14. 1. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University and The Second Clinical Institute of Anhui Medical University, Hefei, China. 2. School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan. 3. Department of Neurology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan. 4. School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan; Department of Life Science, National Taiwan University, Taipei, Taiwan. 5. School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, Taiwan. 6. Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA. 7. Institute of Cognitive Neuroscience, National Central University, Taoyuan, Taiwan; Brain Research Center, National Central University, Taoyuan, Taiwan. 8. Department of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 9. Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 10. Graduate Institute of Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. 11. Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 12. Department of Rehabilitation Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China. 13. Department of Rehabilitation Medicine, The Second Affiliated Hospital of Anhui Medical University and The Second Clinical Institute of Anhui Medical University, Hefei, China. Electronic address: wujianxian@ahmu.edu.cn. 14. School of Physical Therapy and Graduate Institute of Rehabilitation Science, Chang Gung University, Taoyuan, Taiwan; Neuroscience Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan. Electronic address: hsiehth@mail.cgu.edu.tw.
Abstract
BACKGROUND: Transcranial direct current stimulation (tDCS) has been proven to be able to modulate motor cortical plasticity might have potential as an alternative, adjunctive therapy for Parkinson's disease (PD). However, the efficacy of tDCS in PD is still uncertain. A disease animal model may be useful to clarify the existence of a treatment effect and to explore an effective therapeutic strategy using tDCS protocols. OBJECTIVE: The current study was designed to identify the comprehensive therapeutic effects of tDCS in 6-hydroxydopamine (6-OHDA)-lesioned PD rats. METHODS: Following early and long-term tDCS application (starting 24 h after PD lesion, 300 μA anodal tDCS, 20 min/day, 5 days/week) in awake PD animals for a total of 4 weeks, the effects of tDCS on motor and non-motor behaviors as well as dopaminergic neuron degeneration levels, were identified. RESULTS: We found that the 4-week tDCS intervention significantly alleviated 6-OHDA-induced motor deficits in locomotor activity, akinesia, gait pattern and anxiety-like behavior, but not in apomorphine-induced rotations, recognition memory and depression-like behavior. Immunohistochemically, tyrosine hydroxylase (TH)-positive neurons in the substantia nigra were significantly preserved in the tDCS intervention group. CONCLUSIONS: These results suggest that early and long-term tDCS could exert neuroprotective effects and reduce the aggravation of motor dysfunctions in a 6-OHDA-induced PD rat model. Furthermore, this preclinical model may enhance the promising possibility of the potential use of tDCS and serve as a translational platform to further identify the therapeutic mechanism of tDCS for PD or other neurological disorders.
BACKGROUND: Transcranial direct current stimulation (tDCS) has been proven to be able to modulate motor cortical plasticity might have potential as an alternative, adjunctive therapy for Parkinson's disease (PD). However, the efficacy of tDCS in PD is still uncertain. A disease animal model may be useful to clarify the existence of a treatment effect and to explore an effective therapeutic strategy using tDCS protocols. OBJECTIVE: The current study was designed to identify the comprehensive therapeutic effects of tDCS in 6-hydroxydopamine (6-OHDA)-lesioned PDrats. METHODS: Following early and long-term tDCS application (starting 24 h after PD lesion, 300 μA anodal tDCS, 20 min/day, 5 days/week) in awake PD animals for a total of 4 weeks, the effects of tDCS on motor and non-motor behaviors as well as dopaminergic neuron degeneration levels, were identified. RESULTS: We found that the 4-week tDCS intervention significantly alleviated 6-OHDA-induced motor deficits in locomotor activity, akinesia, gait pattern and anxiety-like behavior, but not in apomorphine-induced rotations, recognition memory and depression-like behavior. Immunohistochemically, tyrosine hydroxylase (TH)-positive neurons in the substantia nigra were significantly preserved in the tDCS intervention group. CONCLUSIONS: These results suggest that early and long-term tDCS could exert neuroprotective effects and reduce the aggravation of motor dysfunctions in a 6-OHDA-induced PDrat model. Furthermore, this preclinical model may enhance the promising possibility of the potential use of tDCS and serve as a translational platform to further identify the therapeutic mechanism of tDCS for PD or other neurological disorders.