Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson's Disease.
Milica Zeljkovic JovanovicJelena StanojevicIvana StevanovicAndjela StekićSamuel J BollandNebojsa JasnicMilica NinkovicMarina Zaric KonticTihomir V IlićJennifer RodgerNadezda NedeljkovicMilorad DragicPublished in: Cells (2023)
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the progressive degeneration of the dopaminergic system, leading to a variety of motor and nonmotor symptoms. The currently available symptomatic therapy loses efficacy over time, indicating the need for new therapeutic approaches. Repetitive transcranial magnetic stimulation (rTMS) has emerged as one of the potential candidates for PD therapy. Intermittent theta burst stimulation (iTBS), an excitatory protocol of rTMS, has been shown to be beneficial in several animal models of neurodegeneration, including PD. The aim of this study was to investigate the effects of prolonged iTBS on motor performance and behavior and the possible association with changes in the NMDAR subunit composition in the 6-hydroxydopamine (6-OHDA)-induced experimental model of PD. Two-month-old male Wistar rats were divided into four groups: controls, 6-OHDA rats, 6-OHDA + iTBS protocol (two times/day/three weeks) and the sham group. The therapeutic effect of iTBS was evaluated by examining motor coordination, balance, spontaneous forelimb use, exploratory behavior, anxiety-like, depressive/anhedonic-like behavior and short-term memory, histopathological changes and changes at the molecular level. We demonstrated the positive effects of iTBS at both motor and behavioral levels. In addition, the beneficial effects were reflected in reduced degeneration of dopaminergic neurons and a subsequent increase in the level of DA in the caudoputamen. Finally, iTBS altered protein expression and NMDAR subunit composition, suggesting a sustained effect. Applied early in the disease course, the iTBS protocol may be a promising candidate for early-stage PD therapy, affecting motor and nonmotor deficits.
Keyphrases
- transcranial magnetic stimulation
- high frequency
- early stage
- randomized controlled trial
- parkinson disease
- working memory
- multiple sclerosis
- clinical trial
- oxidative stress
- spinal cord
- traumatic brain injury
- bipolar disorder
- protein kinase
- risk assessment
- stress induced
- cell therapy
- physical activity
- high intensity
- depressive symptoms
- human health
- high glucose
- endothelial cells
- replacement therapy
- sentinel lymph node