Abstract
Repetitive transcranial magnetic stimulation (rTMS) is a popular noninvasive technique for modulating motor cortical plasticity and has therapeutic potential for the treatment of Parkinson's disease (PD). However, the therapeutic benefits and related mechanisms of rTMS in PD are still uncertain. Accordingly, preclinical animal research is helpful for enabling translational research to explore an effective therapeutic strategy and for better understanding the underlying mechanisms. Therefore, the current study was designed to identify the therapeutic effects of rTMS on hemiparkinsonian rats. A hemiparkinsonian rat model, induced by unilateral injection of 6-hydroxydopamine (6-OHDA), was applied to evaluate the therapeutic potential of rTMS in motor functions and neuroprotective effect of dopaminergic neurons. Following early and long-term rTMS intervention with an intermittent theta burst stimulation (iTBS) paradigm (starting 24 h post-6-OHDA lesion, 1 session/day, 7 days/week, for a total of 4 weeks) in awake hemiparkinsonian rats, the effects of rTMS on the performance in detailed functional behavioral tests, including video-based gait analysis, the bar test for akinesia, apomorphine-induced rotational analysis, and tests of the degeneration level of dopaminergic neurons, were identified. We found that four weeks of rTMS intervention significantly reduced the aggravation of PD-related symptoms post-6-OHDA lesion. Immunohistochemically, the results showed that tyrosine hydroxylase- (TH-) positive neurons in the substantia nigra pars compacta (SNpc) and fibers in the striatum were significantly preserved in the rTMS treatment group. These findings suggest that early and long-term rTMS with the iTBS paradigm exerts neuroprotective effects and mitigates motor impairments in a hemiparkinsonian rat model. These results further highlight the potential therapeutic effects of rTMS and confirm that long-term rTMS treatment might have clinical relevance and usefulness as an additional treatment approach in individuals with PD.
Highlights
Parkinson’s disease (PD) is recognized as the second most prevalent age-related neurodegenerative disorder after Alzheimer’s disease, affecting approximately 1% of the population over the age of 60 years [1,2,3,4]
Performances in the detailed video-based gait analysis and bar test were assessed in the 6-Hydroxydopamine brain-derived neurotrophic factor (BDNF) (6-OHDA)+Repetitive transcranial magnetic stimulation (rTMS) treatment group (n = 13) and 6-OHDA+sham treatment group (n = 13) at baseline and every week after the 6-OHDA lesion until the end of the rTMS intervention
With regard to the effect of rTMS on akinesia, we found that four weeks of rTMS in hemiparkinsonian rats led to a reduction in akinesia
Summary
Parkinson’s disease (PD) is recognized as the second most prevalent age-related neurodegenerative disorder after Alzheimer’s disease, affecting approximately 1% of the population over the age of 60 years [1,2,3,4]. The dopamine precursor levodopa is the most common and effective antiparkinsonian medicine and remains the mainstay of PD treatment [10,11,12,13]. With long-term dopaminergic replacement therapy, several complications, mainly motor in nature, such as motor fluctuations, levodopa-induced dyskinesia, freezing, gait disturbance, and postural instability, are common side effects following long-term administration of levodopa [10, 14, 15]. A number of alternative nonpharmacological approaches, e.g., deep-brain stimulation (DBS), have been investigated as new therapeutic strategies for PD [16,17,18,19]. An alternative and better treatment that can modify disease progression is urgently needed for PD
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