Category: Parkinson's Disease: Pathophysiology
Objective: To determine how treadmill exercise impacts behavior and Parkinson-related pathology in the alpha-synuclein (a-syn) preformed fibril (PFF) model.
Background: Exercise is often recommended by physicians for Parkinson disease (PD) patients to facilitate and maintain mobility. Clinical studies show a benefit of exercise on gait, balance, and walking but its neuroprotective potential in the context of neurodegenerative disease has not been established. Preclinical animal studies in toxin models show mixed results regarding the disease-modifying potential of exercise. Determining the effect of exercise on key pathological mechanisms involved in the progression of PD is an important goal in the field. In the present study short-term treadmill exercise was tested in the a-syn PFF rat model of PD to determine effects on behavior and early PD-related pathology in the brain.
Method: Rats received unilateral intrastriatal injections of PFFs or saline (control). Treadmill exercise began one week after PFF injection and animals were trained for 5 days/week for 7 weeks. Control animals remained in the homecage. Behavioral testing was conducted on the last 10 days of treadmill training and included tests for sensorimotor function, emotional reactivity, cognitive function, and olfaction. Postmortem measurements focused on quantification of phosphorylated a-syn (pSyn) inclusions, nigrostriatal system status, neuroinflammation and brain-derived neurotrophic factor (BDNF) levels.
Results: Both control and PFF-treated rats in the exercise group showed decreased bodyweight, increased activity and increased object investigation compared to homecage rats. In movement initiation, a significant deficit in time to make a step was detected in PFF-homecage rats; however, there was no deficit in PFF-exercise compared to control rats. In PFF rats, no effect of exercise was observed on nigral pSyn accumulation, tyrosine hydroxylase immunoreactive neurons or reactive microglia or levels of striatal dopamine. In both exercise and homecage PFF rats, hippocampal BDNF was significantly decreased compared to controls. Analysis of pSyn accumulation in the cortex is ongoing.
Conclusion: Short-term treadmill exercise benefits motor and cognitive function in the a-syn PFF rat model of PD.
To cite this abstract in AMA style:S. Fleming, J. Patterson, C. Kemp, J. Lepp, E. Hamad, S. Scott, J. Holden, A. Davis, C. Szarowicz, J. Lipton, M. Kubik, N. Kuhn, A. Stoll, K. Luk, C. Sortwell. The effect of short-term treadmill exercise in the alpha-synuclein preformed fibril rat model of Parkinson’s disease [abstract]. Mov Disord. 2022; 37 (suppl 2). https://www.mdsabstracts.org/abstract/the-effect-of-short-term-treadmill-exercise-in-the-alpha-synuclein-preformed-fibril-rat-model-of-parkinsons-disease/. Accessed March 5, 2024.
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MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-short-term-treadmill-exercise-in-the-alpha-synuclein-preformed-fibril-rat-model-of-parkinsons-disease/