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Suppression of neuroinflammation and α-synuclein oligomerization by rotarod walking exercise in subacute MPTP model of Parkinson's disease
- Title
- Suppression of neuroinflammation and α-synuclein oligomerization by rotarod walking exercise in subacute MPTP model of Parkinson's disease
- Authors
- Leem Y.-H.; Park J.-S.; Park J.-E.; Kim D.-Y.; Kim H.-S.
- Ewha Authors
- 김희선; 박진선; 임예현
- SCOPUS Author ID
- 김희선; 박진선; 임예현
- Issue Date
- 2023
- Journal Title
- Neurochemistry International
- ISSN
- 0197-0186
- Citation
- Neurochemistry International vol. 165
- Keywords
- Molecular mechanism; Motor skill learning training; Neuroinflammation; Parkinson's disease; Rotarod walking exercise; α-synuclein
- Publisher
- Elsevier Ltd
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Parkinson's disease (PD) belongs to an α-synucleinopathy and manifests motor dysfunction attributed to nigrostriatal dopaminergic degeneration. In clinical practice, the beneficial role of physical therapy such as motor skill learning training has been recognized in PD-linked motor defects. Nevertheless, the disease-modifying effects of motor skill learning training on PD-related pathology remain unclear. Here, we investigated the disease-modifying effects of rotarod walking exercise (RWE), a modality of motor skill learning training, in a subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In motor function and dopaminergic degeneration, RWE improved MPTP-induced deficits. In addition, RWE enhanced the expression of neurotrophic factors BDNF/GDNF, PGC1-α, Nurr1, and p-AMPK, thereby recovering dopaminergic neuronal cell death. Moreover, RWE inhibited microglial activation and the expression of pro-inflammatory markers, such as p-IκBα, iNOS, IL-1β, TNF-α, and cathepsin D, while elevating anti-inflammatory IL-10 and TGF-β. RWE also decreased oxidative stress markers in the substantia nigra, such as 4-HNE and 8-OHdG-positive cells, while increasing Nrf2-controlled antioxidant enzymes. Regarding the effect of RWE on α-synuclein, it reduced the monomer/oligomer forms of α-synuclein and phosphorylation at serine 129. Further mechanistic studies revealed that RWE suppressed the expression of matrix metalloproteinase-3 and p-GSK3β (Y216), which play key roles in α-synuclein aggregation. These data collectively suggest that inhibition of neuroinflammation and α-synuclein oligomerization by RWE may contribute to the improvement of PD pathology. © 2023
- DOI
- 10.1016/j.neuint.2023.105519
- Appears in Collections:
- 의과대학 > 의학과 > Journal papers
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