Neuroplasticity and Neuroprotective Effect of Treadmill Training in the Chronic Mouse Model of Parkinson’s Disease

Abstract

Physical training confers protection to dopaminergic neurons in rodent models of parkinsonism produced by neurotoxins. The sparing effect of physical training on dopaminergic neurons can be tested with training applied during chronic MPTP treatment, while the neurorestorative effect when training is applied after completing such treatment. In this study, the effect of the onset of training respective to chronic MPTP treatment was specifically addressed. Three groups of mice were injected with 10 doses of MPTP (12.5 mg/kg/injection) over 5 weeks. The first group remained sedentary; the second one underwent early onset training, which started 1 week before commencing MPTP treatment, continued throughout 5 weeks of treatment and 4 weeks thereafter; the third group underwent late-onset training of the same length and intensity as the former group, except that it started immediately after the end of MPTP treatment. Two groups served as controls: a saline-injected group that remained sedentary and saline-injected group, which underwent the same training as the early and late-onset training groups. Both early and late-onset physical training saved almost all nigral and VTA dopaminergic neurons, prevented inflammatory response, and increased the BDNF and GDNF levels to a similar extent. From these results one may conclude that early and late-onset training schedules were equipotent in their neuroprotective effect and that the mechanism of neuroprotection was similar. The sparing effect of early onset training may be satisfactorily explained by assuming that the increased level of BDNF and GDNF prevented the degeneration of dopaminergic neurons. To explain a similar number of dopaminergic neurons detected at the end of the early and late-onset training, one should additionally assume that the former training schedule induced neurogenesis. Results of this study support the view that physical activity may be neuroprotective even at a more advanced stage of PD and justify starting physical activity at any point of the disease.

BDNF as a Promising Therapeutic Agent in Parkinson’s Disease

“…Even though a single exercise causes a BDNF increase in the blood of patients with PD, it is short-lived and is not associated with an improvement in the neurological status of the patients. Studies using an animal model of parkinsonism have provided evidence that only the repetition of medium-or high-intensity physical exercise for several weeks or a continuous training process causes an increase in BDNF [179] and TrkB receptor levels [131,180] in the brain regions responsible for motor activity in rats.…”

“…Under the influence of the training process, increased BDNF expression in the hippocampus, cerebral cortex, ST, brainstem, and spinal cord was observed [131,174,179,181,182]. Animal studies have shown that long-term endurance training increased both TrkB receptor and TH expression in structures involved in extrapyramidal movement regulation, i.e., in the ST and midbrain [128,129,179,[183][184][185].…”

“…Physical training protects DA neurons in the SNpc against inflammatory insult [179]. The beneficial effects of exercise are due to the activation of BDNF signaling pathway.…”

Exercise for Older Adults Improves the Quality of Life in Parkinson’s Disease and Potentially Enhances the Immune Response to COVID-19

“…This protocol is moderate-to high-intensity exercise based on the definition of moderate treadmill exercise in mice [74][75][76]. They reported that in both early and late-onset exercise (treadmill) training, there was (a) preservation of dopaminergic neurons in substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), (b) an increase in brain-derived neurotrophic factor in the midbrain and glial cell line-derived neurotrophic factor in the striatum, and (c) mitigation of the pro-inflammatory response in the SNpc and VTA [73].…”

“…In human models, it has been shown that sustained moderate exercise can improve QoL in PD and is likely to help to down-regulate neuroinflammation [12,72,78,[80][81][82][83][84][85][86][87][88][89][90][91]. Going from moderate-to high-intensity exercise (in animal models) further reduces neuroinflammation, which implies neuroprotection [73,77]. O'Callaghan et al showed that high-intensity interval training (HIIT) exercise significantly increased the neuroprotective substance brain-derived neurotrophic factor (BDNF) compared to both moderate-intensity exercise and controls [92].…”