Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease
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 n...
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MDPI AG
2023-06-01
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| author | Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Andjela Stekic Samuel J. Bolland Nebojsa Jasnic Milica Ninkovic Marina Zaric Kontic Tihomir V. Ilic Jennifer Rodger Nadezda Nedeljkovic Milorad Dragic |
| author_facet | Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Andjela Stekic Samuel J. Bolland Nebojsa Jasnic Milica Ninkovic Marina Zaric Kontic Tihomir V. Ilic Jennifer Rodger Nadezda Nedeljkovic Milorad Dragic |
| author_sort | Milica Zeljkovic Jovanovic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T03:10:05Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T03:10:05Z |
| publishDate | 2023-06-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-edccaa63daf9462d9ee6f80958894f552023-11-18T07:41:15ZengMDPI AGCells2073-44092023-06-011211152510.3390/cells12111525Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s DiseaseMilica Zeljkovic Jovanovic0Jelena Stanojevic1Ivana Stevanovic2Andjela Stekic3Samuel J. Bolland4Nebojsa Jasnic5Milica Ninkovic6Marina Zaric Kontic7Tihomir V. Ilic8Jennifer Rodger9Nadezda Nedeljkovic10Milorad Dragic11Laboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Medical Research, Military Medical Academy, 11000 Belgrade, SerbiaInstitute for Medical Research, Military Medical Academy, 11000 Belgrade, SerbiaLaboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaSchool of Biological Sciences, The University of Western Australia, Perth, WA 6009, AustraliaDepartment for Comparative Physiology and Ecophysiology, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaInstitute for Medical Research, Military Medical Academy, 11000 Belgrade, SerbiaDepartment of Molecular Biology and Endocrinology, Vinca Institute of Nuclear Sciences-National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaMedical Faculty of Military Medical Academy, University of Defense, 11000 Belgrade, SerbiaSchool of Biological Sciences, The University of Western Australia, Perth, WA 6009, AustraliaLaboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaLaboratory for Neurobiology, Department for General Physiology and Biophysics, Faculty of Biology, University of Belgrade, 11000 Belgrade, SerbiaParkinson’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.https://www.mdpi.com/2073-4409/12/11/1525Parkinson’s disease6-OHDArTMSiTBSNMDA receptorneuroprotection |
| spellingShingle | Milica Zeljkovic Jovanovic Jelena Stanojevic Ivana Stevanovic Andjela Stekic Samuel J. Bolland Nebojsa Jasnic Milica Ninkovic Marina Zaric Kontic Tihomir V. Ilic Jennifer Rodger Nadezda Nedeljkovic Milorad Dragic Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease Cells Parkinson’s disease 6-OHDA rTMS iTBS NMDA receptor neuroprotection |
| title | Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease |
| title_full | Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease |
| title_fullStr | Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease |
| title_full_unstemmed | Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease |
| title_short | Intermittent Theta Burst Stimulation Improves Motor and Behavioral Dysfunction through Modulation of NMDA Receptor Subunit Composition in Experimental Model of Parkinson’s Disease |
| title_sort | intermittent theta burst stimulation improves motor and behavioral dysfunction through modulation of nmda receptor subunit composition in experimental model of parkinson s disease |
| topic | Parkinson’s disease 6-OHDA rTMS iTBS NMDA receptor neuroprotection |
| url | https://www.mdpi.com/2073-4409/12/11/1525 |
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