Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review
BackgroundThe excitatory imbalance of glutamatergic neurons, caused by insufficient input from dopaminergic neurons, contributes the pathogenesis of Parkinson’s disease (PD). Exercise training is one of the non-pharmacological, non-invasive therapeutic approaches.ObjectiveThis systematic review is t...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1512278/full |
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| author | Shahid Ishaq Iqbal Ali Shah Shin-Da Lee Shin-Da Lee Bor-Tsang Wu |
| author_facet | Shahid Ishaq Iqbal Ali Shah Shin-Da Lee Shin-Da Lee Bor-Tsang Wu |
| author_sort | Shahid Ishaq |
| collection | DOAJ |
| description | BackgroundThe excitatory imbalance of glutamatergic neurons, caused by insufficient input from dopaminergic neurons, contributes the pathogenesis of Parkinson’s disease (PD). Exercise training is one of the non-pharmacological, non-invasive therapeutic approaches.ObjectiveThis systematic review is the first to summarize the effects of exercise training on the regulation of protein and gene expressions within the nigrostriatal glutamatergic pathway and its receptor interactions in animal models of Parkinson’s disease (PD).MethodologyThe PubMed, Web of Science, and Embase electronic databases were searched, and 9 out of 96 studies that met the PRISMA guidelines were included. These studies received a CAMARADES score ranging from 4 to 6 out of 10. The included studies utilized pharmacologically induced PD models in mice or rats with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA). The majority of studies (89%) employed treadmill training, while 11% used voluntary wheel running, with training protocols consisting of 5 days per week for 4 weeks.ResultsExercise training reduced extracellular glutamate (Glu) and increased the expression of GLT-1, GS, Gln, and mGluR2/3 while down-regulating VGULT1 in the presynaptic terminal of the glutamatergic neurons within the nigrostriatal pathway in PD animal models. It also downregulated mGluR5 and modulated the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits: GluA1 was downregulated, inhibiting long-term potentiation, while GluA2 and GluA3 were upregulated in the nigrostriatal pathway in PD animal models. In addition, the exercise training downregulated the N-methyl-D-aspartate (NMDA) receptors, Arc, Cav1.3, CaMKII, and p-CaMKII in the nigrostriatal pathway in PD animal models.ConclusionExercise training exerted a neuroprotective effect on the glutamatergic pathway in Parkinson’s disease (PD) animal models by limiting excess glutamate in the synaptic cleft. Exercise training modulated the ionotropic receptors and limited the glutamatergic excitatory imbalance within the nigrostriatal pathway in PD animal models. It also improved motor function, including balance, coordination, and gait parameters.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024564127 |
| format | Article |
| id | doaj-art-f4bedcf6651746969609f7154697fcd5 |
| institution | Kabale University |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-f4bedcf6651746969609f7154697fcd52025-02-11T06:59:55ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-02-011710.3389/fnagi.2025.15122781512278Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic reviewShahid Ishaq0Iqbal Ali Shah1Shin-Da Lee2Shin-Da Lee3Bor-Tsang Wu4PhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung, TaiwanPhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung, TaiwanPhD Program in Healthcare Science, College of Healthcare Science, China Medical University, Taichung, TaiwanDepartment of Physical Therapy, China Medical University, Taichung, TaiwanDepartment of Senior Citizen Service Management, National Taichung University of Science and Technology, Taichung, TaiwanBackgroundThe excitatory imbalance of glutamatergic neurons, caused by insufficient input from dopaminergic neurons, contributes the pathogenesis of Parkinson’s disease (PD). Exercise training is one of the non-pharmacological, non-invasive therapeutic approaches.ObjectiveThis systematic review is the first to summarize the effects of exercise training on the regulation of protein and gene expressions within the nigrostriatal glutamatergic pathway and its receptor interactions in animal models of Parkinson’s disease (PD).MethodologyThe PubMed, Web of Science, and Embase electronic databases were searched, and 9 out of 96 studies that met the PRISMA guidelines were included. These studies received a CAMARADES score ranging from 4 to 6 out of 10. The included studies utilized pharmacologically induced PD models in mice or rats with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine (6-OHDA). The majority of studies (89%) employed treadmill training, while 11% used voluntary wheel running, with training protocols consisting of 5 days per week for 4 weeks.ResultsExercise training reduced extracellular glutamate (Glu) and increased the expression of GLT-1, GS, Gln, and mGluR2/3 while down-regulating VGULT1 in the presynaptic terminal of the glutamatergic neurons within the nigrostriatal pathway in PD animal models. It also downregulated mGluR5 and modulated the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits: GluA1 was downregulated, inhibiting long-term potentiation, while GluA2 and GluA3 were upregulated in the nigrostriatal pathway in PD animal models. In addition, the exercise training downregulated the N-methyl-D-aspartate (NMDA) receptors, Arc, Cav1.3, CaMKII, and p-CaMKII in the nigrostriatal pathway in PD animal models.ConclusionExercise training exerted a neuroprotective effect on the glutamatergic pathway in Parkinson’s disease (PD) animal models by limiting excess glutamate in the synaptic cleft. Exercise training modulated the ionotropic receptors and limited the glutamatergic excitatory imbalance within the nigrostriatal pathway in PD animal models. It also improved motor function, including balance, coordination, and gait parameters.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42024564127https://www.frontiersin.org/articles/10.3389/fnagi.2025.1512278/fullglutamateglutamatergic systemglutamate receptorsnigrostriatumParkinson’s diseaseParkinson |
| spellingShingle | Shahid Ishaq Iqbal Ali Shah Shin-Da Lee Shin-Da Lee Bor-Tsang Wu Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review Frontiers in Aging Neuroscience glutamate glutamatergic system glutamate receptors nigrostriatum Parkinson’s disease Parkinson |
| title | Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review |
| title_full | Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review |
| title_fullStr | Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review |
| title_full_unstemmed | Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review |
| title_short | Effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in Parkinson’s disease: a systematic review |
| title_sort | effects of exercise training on the nigrostriatal glutamatergic pathway and receptor interactions in parkinson s disease a systematic review |
| topic | glutamate glutamatergic system glutamate receptors nigrostriatum Parkinson’s disease Parkinson |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1512278/full |
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