Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity
Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intens...
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| Veröffentlicht in: | Science advances Jg. 9; H. 28; S. eadh1403 |
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| Sprache: | Englisch |
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American Association for the Advancement of Science
14.07.2023
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| ISSN: | 2375-2548, 2375-2548 |
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| Abstract | Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of
N
-methyl-
d
-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.
Intensive exercise reshapes functional and structural aspects of corticostriatal synapses in an α-syn-based animal model of PD. |
|---|---|
| AbstractList | Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of
N
-methyl-
d
-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.
Intensive exercise reshapes functional and structural aspects of corticostriatal synapses in an α-syn-based animal model of PD. Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of N-methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas. Intensive exercise reshapes functional and structural aspects of corticostriatal synapses in an α-syn-based animal model of PD. Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of -methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas. Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of N-methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas.Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the beneficial effects of exercise on PD-associated neuronal alterations have not been fully clarified yet. Here, we tested the hypothesis that an intensive treadmill training program rescues alterations in striatal plasticity and early motor and cognitive deficits in rats receiving an intrastriatal injection of alpha-synuclein (α-syn) preformed fibrils. Improved motor control and visuospatial learning in active animals were associated with a recovery of dendritic spine density alterations and a lasting rescue of a physiological corticostriatal long-term potentiation (LTP). Pharmacological analyses of LTP show that modulations of N-methyl-d-aspartate receptors bearing GluN2B subunits and tropomyosin receptor kinase B, the main brain-derived neurotrophic factor receptor, are involved in these beneficial effects. We demonstrate that intensive exercise training has effects on the early plastic alterations induced by α-syn aggregates and reduces the spread of toxic α-syn species to other vulnerable brain areas. |
| Author | Calabresi, Paolo Marino, Gioia De Carluccio, Maria Servillo, Federica Crupi, Francesco Gardoni, Fabrizio Natale, Giuseppina Picconi, Barbara Campanelli, Federica Viscomi, Maria Teresa Caristo, Maria Emiliana De Leonibus, Elvira Ferrari, Elena Ghiglieri, Veronica Cardinale, Antonella Loffredo, Vittorio |
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| Cites_doi | 10.1046/j.0953-816x.2001.01485.x 10.1002/ana.26291 10.1038/nrdp.2017.13 10.1038/nn1040 10.1002/brb3.2628 10.1016/S1474-4422(19)30285-6 10.1016/j.neuroscience.2017.05.016 10.1111/j.1460-9568.1992.tb00119.x 10.1093/brain/awz065 10.1002/brb3.2544 10.1074/jbc.M113.482000 10.1038/42166 10.1016/S1474-4422(13)70123-6 10.1001/jamaneurol.2017.3517 10.1093/brain/awab242 10.1523/JNEUROSCI.20-22-08443.2000 10.1002/mds.28671 10.1093/brain/116.2.433 10.1016/j.nbd.2015.11.022 10.1038/npp.2008.129 10.1002/mds.27865 10.1002/mds.27683 10.1186/s40035-021-00254-1 10.1038/nn.3743 10.1093/brain/awx351 10.1016/j.celrep.2022.111058 10.1016/j.expneurol.2016.10.009 10.1016/j.brainres.2015.01.016 10.1007/s00213-007-0862-4 10.1073/pnas.1713969114 10.1038/ncomms3031 10.1016/j.phrs.2022.106375 10.1016/j.bbr.2016.12.009 10.1007/s10571-010-9523-y 10.1016/S1353-8020(09)70805-3 10.1523/JNEUROSCI.2664-12.2012 10.12965/jer.1734906.453 10.1016/S0169-328X(97)00349-5 10.1038/s41572-021-00280-3 10.1016/B978-0-12-819410-2.00008-4 10.1016/j.lfs.2020.117345 |
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| Snippet | Intensive physical activity improves motor functions in patients with Parkinson’s disease (PD) at early stages. However, the mechanisms underlying the... Intensive physical activity improves motor functions in patients with Parkinson's disease (PD) at early stages. However, the mechanisms underlying the... |
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| SubjectTerms | Animals Cognition Corpus Striatum Diseases and Disorders Long-Term Potentiation - physiology Neuronal Plasticity - physiology Neuroscience Parkinson Disease - therapy Rats SciAdv r-articles |
| Title | Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson’s disease restoring striatal synaptic plasticity |
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