Dataset Information

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats.

ABSTRACT:

Background

Rodent Parkinson's disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient.

Objective

To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact.

Method

We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr ≤1.5) exercising in non-contact boxing training for ≥3 months, ≥3x/week. In 4-month-old Pink1 knockout (KO) rats exercising in a progressively-increased treadmill speed regimen, we determined a specific treadmill speed that increased HR to an extent similar in human subjects.

Results

After completing aerobic exercise for ∼30 min, PD subjects had increased HR∼35% above baseline (∼63% maximum HR). Motor and cognitive test results indicated the exercising subjects completed the timed up and go (TUG) and trail-making test (TMT-A) in significantly less time versus exercise-naïve PD subjects. In KO and age-matched wild-type (WT) rats, treadmill speeds of 8-10 m/min increased HR up to 25% above baseline (∼67% maximum HR), with no further increases up to 16 m/min. Exercised KO, but not WT, rats showed increased locomotor activity compared to an age-matched exercise-naïve cohort at 5 months old.

Conclusion

These proof-of-concept results indicate HR is a cross-species translation parameter to evaluate aerobic exercise impact on specific motor or cognitive functions in human subjects and rat PD models. Moreover, a moderate intensity exercise regimen is within the physical abilities of early-stage PD patients and is therefore applicable for interrogating neurobiological mechanisms in rat PD models.

SUBMITTER: Salvatore MF

PROVIDER: S-EPMC9535586 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats.

Salvatore Michael F MF Soto Isabel I Kasanga Ella A EA James Rachael R Shifflet Marla K MK Doshier Kirby K Little Joel T JT John Joshia J Alphonso Helene M HM Cunningham J Thomas JT Nejtek Vicki A VA

Journal of Parkinson's disease 20220101 6

<h4>Background</h4>Rodent Parkinson's disease (PD) models are valuable to interrogate neurobiological mechanisms of exercise that mitigate motor impairment. Translating these mechanisms to human PD must account for physical capabilities of the patient.<h4>Objective</h4>To establish cardiovascular parameters as a common metric for cross-species translation of aerobic exercise impact.<h4>Method</h4>We evaluated aerobic exercise impact on heart rate (HR) in 21 early-stage PD subjects (Hoehn Yahr ≤1 ...[more]

PMID: 35754287

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Project description:Preclinical models of Parkinson's disease are imperative to gain insight into the neural circuits that contribute to gait dysfunction in advanced stages of the disease. A PTEN-induced putative kinase 1 knockout early-onset model of Parkinson's disease may be a useful rodent model to study the effects of neurotransmitter degeneration caused by a loss of PTEN-induced putative kinase 1 function on brain activity during volitional gait. The goal of this study was to measure changes in neural activity at the cerebellar vermis at 8 months of age. It was found that gait deficits, except run speed, were not significantly different from age-matched wild-type controls, as previously reported. PTEN-induced putative kinase 1 knockout (n = 4) and wild-type (n = 4) rats were implanted with a micro-electrocorticographic array placed over cerebellar vermis Lobules VI (a-c) and VII. Local field potential recordings were obtained during volitional gait across a runway. Power spectral analysis and coherence analysis were used to quantify network oscillatory activity in frequency bands of interest. Cerebellar vermis power was hypoactive in the beta (VIb, VIc and VII) and alpha (VII) bands at cerebellar vermis Lobules VIb, VIc and VII in PTEN-induced putative kinase 1 knockout rats compared with wild-type controls during gait (P < 0.05). These results suggest that gait improvement in PTEN-induced putative kinase 1 knockout rats at 8 months may be a compensatory mechanism attributed to movement corrections caused by a decreased inhibition of the alpha band of cerebellar vermis Lobule VII and beta band of Lobules VIb, VIc and VII. The PTEN-induced putative kinase 1 knockout model may be a valuable tool for understanding the circuit mechanisms underlying gait dysfunction in patients with early-onset Parkinson's disease with a functional loss of PTEN-induced putative kinase 1. Future studies investigating the cerebellar vermis as a potential biomarker and therapeutic target for the treatment of gait dysfunction in Parkinson's disease are warranted.

Project description:Parkinson's disease (PD) is a progressive neurological disorder characterized by motor and non-motor symptoms for which only symptomatic treatments exist. Exercise is a widely studied complementary treatment option. Aerobic exercise, defined as continuous movement of the body's large muscles in a rhythmic manner for a sustained period that increases caloric requirements and aims at maintaining or improving physical fitness, appears promising. We performed both a scoping review and a systematic review on the generic and disease-specific health benefits of aerobic exercise for people with PD. We support this by a meta-analysis on the effects on physical fitness (VO2max), motor symptoms (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor section), and health-related quality of life (39-item Parkinson's disease Questionnaire (PDQ-39)). Aerobic exercise has generic health benefits for people with PD, including a reduced incidence of cardiovascular disease, a lower mortality, and an improved bone health. Additionally, there is level 1 evidence that aerobic exercise improves physical fitness (VO2max) and attenuates motor symptoms (MDS-UPDRS motor section) in the off-medication state, although the long-term effects (beyond 6 months) remain unclear. Dosing the exercise matters: improvements appear to be greater after training at higher intensities compared with moderate intensities. We found insufficient evidence for a beneficial effect of aerobic exercise on health-related quality of life (PDQ-39) and conflicting results regarding non-motor symptoms. Compliance to exercise regimes is challenging for PD patients but may be improved by adding exergaming elements to the training program. Aerobic exercise seems a safe intervention for people with PD, although care must be taken to avoid falls in at-risk individuals. Further studies are needed to establish the long term of aerobic exercise, including a focus on non-motor symptoms and health-related quality of life.

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Dataset Information

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats.

Background

Objective

Method

Results

Conclusion

Publications

Establishing Equivalent Aerobic Exercise Parameters Between Early-Stage Parkinson's Disease and Pink1 Knockout Rats.

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