Transcranial Magnetic Stimulation Attenuates Dyskinesias and FosB and c-Fos Expression in a Parkinson’s Disease Model

Abstract

Background/Objectives: Dopamine replacement therapy for Parkinson’s disease (PD) may lead to disabling incontrollable movements known as L-DOPA-induced dyskinesias. Transcranial magnetic stimulation (TMS) has been applied as non-invasive therapy to ameliorate motor symptoms and dyskinesias in PD treatment. Recent studies have shown that TMS-induced motor effects might be related to dopaminergic system modulation. However, the mechanisms underlying these effects of TMS are not fully understood. Objectives: To assess the expression of FosB and c-Fos in dopamine-D1 receptor-containing cells of dyskinetic rats and to analyze the effect of TMS on dyskinetic behavior and its histological marker (FosB). Methods: We investigated the outcome of TMS on cellular activation, using c-Fos immunoreactivity, on D1 receptor-positive (D1R+) cells into the motor cortex and striatum of dyskinetic (n = 14) and intact rats (n = 14). Additionally, we evaluated the effect of TMS on the dyskinesia global score and its molecular marker, FosB, in the striatum (n = 67). Results: TMS reduces c-Fos expression in D1R+cells into the motor cortex and striatum. Moreover, TMS treatment attenuated dyskinesias, along with a low stratal FosB expression. Conclusions: The current study shows that TMS depressed FosB and c-Fos expression in D1R+ cells of the dorsal striatum and motor cortex, in accordance with previous evidence of its capacity to modulate the dopaminergic system, thus suggesting a mechanism by which TMS may mitigate dyskinesias. Additionally, our observations highlight the potential therapeutic effect of TMS on dyskinesias in a PD model.