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Treadmill Exercise Alleviates Motor Deficits of PD Mice via Regulating STING-Mediated Valeric Acid-Th17/Treg-IL-17A
Xiaoqian Liu1, Menglin Lv1, Dekun Liu1
1College of Sports Medicine, Wuhan Sports University, Wuhan, 430079, China.
Molecular Neurobiology
|June 3, 2026
Summary
Treadmill exercise significantly improves motor function in Parkinson's disease (PD) mice by enhancing gut health and reducing inflammation. These benefits are linked to STING signaling, short-chain fatty acids, and improved gut-brain barrier integrity.
Area of Science:
- Neuroscience
- Immunology
- Gastroenterology
Background:
- Parkinson's disease (PD) is characterized by motor deficits and neuroinflammation.
- The gut-brain axis and immune system play crucial roles in PD pathogenesis.
- Current treatments for PD have limitations, necessitating exploration of novel therapeutic strategies.
Purpose of the Study:
- To investigate the efficacy of treadmill exercise in ameliorating motor deficits in a mouse model of chronic PD.
- To elucidate the underlying mechanisms, including the role of short-chain fatty acids (SCFAs), immune balance, and gut-brain barrier integrity.
- To examine the involvement of STING (stimulator of interferon genes) signaling in exercise-induced therapeutic effects.
Main Methods:
- MPTP/p-induced chronic PD mouse model.
- Assessment of motor function using gait analysis, rota-rod, wire hang, pole, and open field tests.
- Analysis of fecal SCFAs, colonic morphology, gut barrier integrity, blood-brain barrier (BBB) function, and immune markers (Th17/Treg balance, inflammation) via GC-MS, histology, immunofluorescence, Western blot, qPCR, and ELISA.
Main Results:
- Treadmill exercise significantly improved motor function and increased fecal valeric acid levels in PD mice.
- Exercise ameliorated Th17/Treg immune imbalance, improved gut barrier and BBB integrity, and reduced colon and brain inflammation.
- The STING agonist DMXAA abolished the beneficial effects of treadmill exercise, indicating STING's crucial role.
- DMXAA administration blunted exercise-induced improvements in motor dysfunction, gut health, and immune balance.
Conclusions:
- Treadmill exercise is a promising non-pharmacological intervention for improving motor function in chronic PD.
- The therapeutic effects of exercise are mediated by STING-dependent pathways involving SCFAs, immune modulation (Th17/Treg balance), and restoration of gut and blood-brain barrier integrity.
- Targeting the gut-brain axis and STING signaling may offer novel therapeutic avenues for Parkinson's disease.
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