Author(s): YOOK, J., HWANG, DJ., LEE, HS., Institution: POHANG UNIVERSITY OF SCIENCE AND TECHNOLOGY (POSTECH), Country: KOREA, SOUTH, Abstract-ID: 966

INTRODUCTION:
Parkinson’s disease (PD) is a hallmark neurodegenerative disorder characterized by dopamine depletion in the substantia nigra, resulting in primary motor dysfunctions such as tremors and gait disturbances. Although exercise intervention is recognized as a complementary therapy in treating the progressive motor impairment of PD, its clinical application is limited by a lack of research on specific exercise intensities in animal models of PD. Despite recognizing the benefits of exercise in both rodent models and human patients with PD, the efficacy of these interventions is highly dependent on exercise intensity. From a translational research perspective, this study aims to identify the optimal exercise intensity based on ventilatory threshold for preventing motor impairments in a 6-hydroxydopamine (6-OHDA) mouse model of PD.
METHODS:
To induce PD-like motor symptoms, 6-OHDA was unilaterally administered into the medial forebrain bundle of C57BL/6J male mice. Sham mice were unilaterally injected with saline. Exercise intensity was determined by ventilatory threshold (VT) as a key physiological marker of aerobic exercise [1]. After a 1-week treadmill training phase, an incremental treadmill running test was performed to monitor gas exchange of oxygen uptake (VO2) and carbon dioxide output (VCO2) using a metabolic chamber. For verification of VT-based exercise intensity, blood lactate levels were measured following a single bout of running at various intensities; light (sub-VT), moderate (at VT), and vigorous (supra-VT). Subsequently, the 6-OHDA mice underwent exercise training at different intensities. Motor behaviours were assessed via Rotarod and Pole tests at 4 weeks of exercise period.
RESULTS:
Results showed that 6-OHDA mice exhibited significantly lower VO2 (p < 0.001) and VCO2 (p < 0.01) during incremental loading compared to Sham mice. The treadmill running speed at VT was 10 m/min for 6-OHDA mice, a significant decrease from the 13.6 m/min observed in Sham mice (p < 0.01). Blood lactate levels after a single bout of running were significantly elevated in the supra-VT compared to the sub-VT in both Sham and 6-OHDA mice (p < 0.05). Furthermore, a 4-week intervention of vigorous exercise was found to be the most effective intensity for enhancing behavioral outcomes in the Rotarod and Pole tests.
CONCLUSION:
These results demonstrate the establishment of different exercise intensities based on VT for the 6-OHDA mouse model of PD. An exercise intervention optimized with appropriate intensity effectively prevents motor dysfunction in PD. Thus, an optimal exercise regimen can serve as a beneficial complement to maximize the pharmacologic or surgical therapeutic effects for PD.

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