Deciphering Physiological and Therapeutic Roles of Transcranial Direct Current Stimulation (Tdcs) in Motor and Cognitive Impairments Using Parkinsonian Rat Model

Project: National Science and Technology CouncilNational Science and Technology Council Academic Grants

Project Details

Abstract

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorder which affects approximately 7-10 million individuals people worldwide and thirty thousand people in Taiwan, respectively. The pathologic hallmark of the disease are the loss of the nigrostriatal dopaminergic neurons and causes to several motor disturbance, such as tremor, rigidity, akinesia, and gait disturbance. In addition to classical motor symptoms, it is nowadays widely recognized that PD is much more than a motor disorder. Non-motor symptoms, such as cognitive impairment, depression, anxiety and memory loss are gaining increasing attention. Although pharmaceutical agents have been quite successful in the management of PD, the symptom relief is often incomplete, and chronic drug therapy is often limited by side-effects. Thus, new therapeutic and alternative strategies are clearly needed for PD. Non-invasive brain stimulation technique such as transcranial direct current stimulation (tDCS), has been increasingly developed for modulating cortical plasticity which is considered having therapeutic potentials in PD. However, the therapeutic values of such approach for PD are still uncertain and controversial. Accordingly, a disease animal model may be useful to clarify the existence of treatment effect and explore an effective therapeutic strategy using tDCS protocols. This proposed project is aimed to identify the therapeutic potential of tDCS in a PD animal model, as an early step toward possible eventual clinical. To achieve these goals, the neurotoxic PD rats induced by 6-hydroxydopamine (6-OHDA) will be applied to evaluate the therapeutic potential of tDCS at three major levels: behavioral (as measured by targeted tasks), electrophysiology (as reflected in cortical function) and molecular (as assayed by immunohistochemistry). In the first year, we will design the long-term implantable tDCS module for stimulating a specific area of the cerebral cortex in freely moving PD rats. The dysfunctions of neuroplasticity and neuromodulation in PD rats will be verified by electrophysiological measurements of electroencephalography (EEG) and motor evoked potential (MEP). Several quantitative platforms will be adapted to assess the motor (e.g., rigidity, tremor, akinesia, gait) and non-motor (depression, anxiety, recognition memory loss) impairments with disease progression. In the second year, to validate and optimize the protocols of tDCS, PD rat model will be chronically treated with tDCS, followed by monitoring the degeneration in motor and non-motor functions. Pathological analyses on dopaminergic neurons degeneration level will also be conducted. Furthermore, the obtained EEG results will provide detailed guidance that can help to determine the protocols and stimulated areas of the tDCS for PD. In the last year, with the help of this model, the therapeutic effects of long-term tDCS treatment for improving neuroprotection and neurogenesis in PD rats will be verified. This integrated evaluated and therapeutic approaches will provide a unique opportunity to detect the beneficial effects of neuroplasticity, neuromodulation as well as motor/cognitive function after tDCS interventions in the PD rat model, which may enhance for promising possibility of potential use of tDCS and may serve as a translational platform bridging human and animal studies for developing therapeutic strategies of tDCS for PD or other neurological disorders.

Project IDs

Project ID:PF10607-0957
External Project ID:MOST106-2410-H182-008-MY2
StatusFinished
Effective start/end date01/08/1731/07/18

Keywords

  • Transcranial direct current stimulation
  • Parkinson’s disease
  • motor function

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