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.
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http://dx.doi.org/10.1016/j.neuint.2023.105519 | DOI Listing |
Paediatr Drugs
January 2025
Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
Oral ganaxolone (ZTALMY), a synthetic analogue of the endogenous neuroactive steroid allopregnanolone, acts as a positive allosteric modulator of synaptic and extra-synaptic γ-aminobutyric acid (GABA) type A receptor function in the CNS. In the EU and the UK, it is approved for the adjunctive treatment of epileptic seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients aged 2-17 years. In a multinational phase III study (Marigold), 17 weeks' therapy with adjunctive ganaxolone, administered orally three times daily with food, significantly reduced 28-day major motor seizure frequency from baseline versus placebo in patients aged 2-19 years with CDD-associated refractory epilepsy.
View Article and Find Full Text PDFHealthcare (Basel)
December 2024
Department of Public Health, Semey Medical University, Semey City 071400, Kazakhstan.
Objectives: This study investigated stroke survivors and the characteristics of care management after discharge from hospital to home. The study aimed to identify caregiving difficulties and to assess mastery of skills in implementing recovery activities at home. This was a cross-sectional study.
View Article and Find Full Text PDFChild Adolesc Ment Health
January 2025
School of Public Health, Southeast University, Nanjing, China.
Background: Animal-assisted interventions (AAIs) have emerged as a promising nonpharmacological intervention option for children diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, recent systematic reviews have been primarily narrative. Additionally, the pooled effectiveness of AAIs was absent from these systematic reviews.
View Article and Find Full Text PDFBMC Pediatr
January 2025
China Athletics College, Beijing Sport University, Beijing, China.
Background And Objectives: Obese and overweight children and adolescents exhibit significant deficits in inhibitory function compared to their typical-weight peers. There is a high variability in the effectiveness of exercise interventions on inhibitory function in obese and overweight children and adolescents, and clinical protocols lack consistency. This study aims to systematically review the effects of exercise interventions on inhibitory function in obese and overweight children and adolescents.
View Article and Find Full Text PDFBMJ Paediatr Open
January 2025
School of Health Sciences, University of Dundee, Dundee, UK
Background: Early child development sets the course for optimal outcomes across life. Increasing numbers of children worldwide are exposed to opioids in pregnancy and frequently live in environments associated with adverse developmental outcomes. Although multiple systematic reviews have been published in this area, they use different exposures and different types of outcomes.
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