Sedentary Parkinson's Disease Research Articles

Endurance exercise training suppresses myostatin upregulation and nuclear factor-kappa B activation in a mouse model of Parkinson's disease.

Background and Aim:Muscle atrophy is common in Parkinson’s disease (PD). Although myostatin has been implicated in muscle atrophy, its expression in PD skeletal muscle has not been investigated. Therefore, this study aimed to elucidate the influence of PD induction and exercise training on myostatin expression in the gastrocnemius skeletal muscle.Materials and Methods:Thirty albino mice were randomly selected and separated into three groups of 10 mice each: Sedentary control, sedentary PD (SPD), and exercised PD (EPD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid were used to induce chronic parkinsonism in the PD groups. Immunohistochemistry was used to investigate the expression of myostatin and nuclear factor kappa B (NF-kB) in gastrocnemius muscles of all three groups.Results:Myostatin expression and NF-kB nuclear localization, indicative of its activation, were significantly (p<0.01) higher in gastrocnemius skeletal muscle in the SPD group than in the control and EPD groups. Concomitantly, the average cross-sectional area of gastrocnemius muscle fibers in the SPD albino mice was significantly smaller (p<0.01) than in the control and EPD groups, indicating muscle atrophy.Conclusion:The present data are the first to indicate a correlation between PD induction and myostatin overexpression and NF-kB activation in the gastrocnemius muscle, potentially promoting the muscle atrophy commonly seen in PD. Additionally, the current data are the first to indicate the beneficial effects of exercise training on PD-associated myostatin overexpression, NF-κB activation, and muscle atrophy. Thus, our data are the first to suggest that myostatin and NF-κB might be regarded as potential therapeutic targets in an attempt to ameliorate skeletal muscle abnormalities commonly observed in PD.

Treadmill exercise training could attenuate the upregulation of Interleukin-1 beta and tumor necrosis factor alpha in the skeletal muscle of mouse model of chronic/progressive Parkinson disease.

Induction of Parkinson disease (PD) causes interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) upregulation in gastrocnemius skeletal muscles. Endurance exercise suppresses iNOS and HSP90 overexpression in PD skeletal muscle. The purpose of this study is to test the impact of treadmill exercise training on PD-associated IL-1β and TNF-α upregulation in the gastrocnemius muscle. Thirty normal albino mice were randomly selected and divided into three equal groups: sedentary control (SC), sedentary PD (SPD), and Exercised PD (EPD). Chronic Parkinsonism was induced by treating mice in the SPD and EPD groups with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and probenecid (MPTP/p). Gastrocnemius muscles were examined for the expression of IL-1β and TNF-α using immunohistochemistry in the three different groups. Endurance exercise training significantly decreased both IL-1β and TNF-α expression in skeletal muscle in EPD (P value < 0.01) compared with that in the SPD. Our present data suggest that PD-induced upregulation of IL-1β and TNF-α in the gastrocnemius muscle could be reversed following endurance exercise training. Accordingly, IL-1β and TNF-α might be considered therapeutically to ameliorate skeletal muscle abnormalities characterizing PD.

Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the gradual loss of cells in substantia nigra. Nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of nervous system. The aims of this study are: 1) To investigate the expression of the inducible form of NO (iNOS), and compare it to neuronal nitric oxide (nNOS) in the brain of a chronic mouse model of PD and 2) To study the effect of endurance exercise training on the expression of these markers.METHODMouse models of PD were obtained using 10 doses of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Forty C57BL/6 albino mice were randomly divided into four groups: sedentary control (SC, N = 10), exercise control (EC, N = 10), sedentary PD (SPD, N = 10), exercise PD (EPD, N = 10). At the end of training program, nNOS and iNOS were evaluated in the striatum in all animal groups using immunohistochemistry.RESULTSnNOS showed significant increases in striatum (ST) of SPD mice compared to SC mice (P &gt; 0.03). There was also decreased expression of nNOS in EC group compared to SC mice, but this decrease was not significant (P &gt; 0.8). Exercise training significantly decreased the level of nNOS in the EPD compared to SPD, (P &gt; 0.04). Although, iNOS expression followed almost the same trend as nNOS, but exercise training did not significantly decrease the expression of iNOS in both EC and EPD groups, P &gt; 0.2 and 0.3 respectively.DISCUSSIONThe data from this study suggests that 4 weeks of treadmill exercise has a positive impact on the expression of nNOS and iNOS in the striatum of a PD model. This might clear in part the pathogenicity of the diseases and the positive impact of training on PD.Support or Funding InformationThis work was funded from the Deanship of Scientific Research at Jordan University of Science and TechnologyThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Evaluation of implementation of the ParkFit program: A multifaceted intervention aimed to promote physical activity in patients with Parkinson's disease

ObjectivesWe recently completed the ParkFit study, a two-year randomized controlled trial including 586 sedentary Parkinson's disease (PD) patients, that evaluated a multifaceted intervention (ParkFit program) to promote physical activity. The results showed that the ParkFit program enables PD patients to become physically more active, suggesting that this intervention should now be further implemented into clinical practice. To facilitate this process, we here evaluate the implementation of the ParkFit program. MethodsThe ParkFit program was evaluated in three ways: (a) experiences of patients and physiotherapists, as investigated using interviews and questionnaires; (b) factors associated with changed activity levels; and (c) subgroup analyses to identify differential effects in subgroups of patients based on baseline physical activity level, age, gender, disease severity, disease duration, and mobility. ResultsThe ParkFit program was well received: 73% of patients indicated they would recommend the program to other patients, and 90% of physiotherapists indicated they wanted to use the ParkFit program in other patients. Multiple forward regression analysis resulted in a model with two variables: less baseline physical activity, and better mobility were associated with larger changes in levels of physical activity (R2=38%). The program was effective in almost all subgroups. In women, most sedentary patients and patients with higher disease severity, the estimated effect size was largest. ConclusionWe conclude that the ParkFit program was effective in almost all specific subgroups. Therapists and patients experienced no major hurdles. Suggestions for improvement are: (1) improve education for therapists with respect to theories about behavioral change; (2) formulate concrete and specific examples of exercise goals; and (3) pay more specific attention to patients with co morbidities, cognitive dysfunction and a lack of motivation during education

Quantifying daily physical activity and determinants in sedentary patients with Parkinson's disease

BackgroundAlthough physical activity is beneficial for Parkinson's disease (PD) patients, many do not meet the recommended levels. The range of physical activity among sedentary PD patients is unknown, as are factors that determine this variability. Hence, we aimed to (1) assess daily physical activity in self-identified sedentary PD patients; (2) compare this with criteria of a daily physical activity guideline; and (3) identify determinants of daily physical activity. MethodsDaily physical activity of 586 self-identified sedentary PD patients was measured with a tri-axial accelerometer for seven consecutive days. Physical fitness and demographic, disease-specific, and psychological characteristics were assessed. Daily physical activity was compared with the 30-min activity guideline. A linear mixed-effects model was estimated to identify determinants of daily physical activity. ResultsAccelerometer data of 467 patients who fulfilled all criteria revealed that >98% of their day was spent on sedentary to light-intensity activities. Eighty-two percent of the participants were ‘physically inactive’ (0 days/week of 30-min activity); 17% were ‘semi-active’ (1–4 days/week of 30-min activity). Age, gender, physical fitness, and scores on the Unified Parkinson's Disease Rating Scale explained 69% of the variability in daily physical activity. ConclusionsPerformance-based measurements confirmed that most self-identified sedentary PD patients are ‘physically inactive’. However, the variance in daily physical activity across subjects was considerable. Higher age, being female, and lower physical capacity were the most important determinants of reduced daily physical activity. Future therapeutic interventions should aim to improve daily physical activity in these high-risk patients, focusing specifically on modifiable risk factors.

Coaching and Physiotherapy for Sedentary Parkinson Disease Patients

To examine the effects of a behavioral change–based exercise program (ParkFit) compared with standard physiotherapy for Parkinson disease (PD),

Endurance exercise training protects against the upregulation of nitric oxide in the striatum of MPTP/probenecid mouse model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the gradual loss of cells in substantia nigra. Nitric oxide (NO) plays an important role in a variety of signal transduction pathways that are crucial for maintaining the physiologic functions of nervous system. The aims of this study are: 1) To investigate the expression of the inducible form of NO (iNOS), and compare it to neuronal nitric oxide (nNOS) in the brain of a chronic mouse model of PD and 2) To study the effect of endurance exercise training on the expression of these markers. Mouse models of PD were obtained using 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Forty C57BL /6 albino mice were randomly divided into four groups: sedentary control (SC, N = 10), exercise control (EC, N = 10), sedentary PD (SPD, N = 10), exercise PD (EPD, N = 10). At the end of training program, nNOS and iNOS were evaluated in the striatum in all animal groups using immunohistochemistry. nNOS showed significant increases in striatum (ST) of SPD mice compared to SC mice (P > 0.03). There was also decreased expression of nNOS in EC group compared to SC mice, but this decrease was not significant (P > 0.8). Exercise training significantly decreased the level of nNOS in the EPD compared to SPD, (P > 0.04). Although, iNOS expression followed almost the same trend as nNOS, but exercise training did not significantly decrease the expression of iNOS in both EC and EPD groups, P > 0.2 and 0.3 respectively. The data from this study suggests that 4 weeks of treadmill exercise has a positive impact on the expression of nNOS and iNOS in the striatum of a PD model. This might clear in part the pathogenicity of the diseases and the positive impact of training on PD.

Cardiovascular Responses During a Submaximal Exercise Test in Patients with Parkinson's Disease

Patients with Parkinson's disease (PD) are physically less active than controls, and autonomic dysfunction may contribute to this sedentary lifestyle. Specifically, an altered cardiovascular response to physical effort may restrict physical activities. To assess the cardiovascular responses to a submaximal exercise test in PD patients and controls, 546 sedentary PD patients and 29 sedentary healthy controls performed the Åstrand-Rhyming submaximal cycle exercise test. Average heart rate was used to estimate maximal oxygen consumption (VO2max). Variables that may affect submaximal activity in PD patients, including disease severity, fatigue, and level of physical activity in daily life, were recorded. Fewer PD patients (46%) completed the submaximal exercise test successfully than the controls (86%). The estimated VO2max of patients with a successful test was 34% lower than the controls (p < 0.001). Multivariate regression analyses revealed that higher body weight, lower systolic blood pressure, lower resting heart rate, and lower maximal workload were associated with an increased risk of an inadequate heart rate increase during submaximal exercise (R2 = 27%). PD patients with a successful submaximal exercise test had lower estimated VO2max values than controls. Importantly, half of the PD patients had an inadequate heart rate increase during submaximal exercise, which was likely caused by cardiac sympathetic denervation leading to autonomic dysfunction. PD patients should therefore be screened to identify their limitations in exercise performance. Caution should be applied when prescribing beta blockers, as they might limit physical activities further.

Effect of endurance exercise training on the expression of GFAP, S100B, and NSE in the striatum of chronic/progressive mouse model of Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in elderly. Glial fibrillary acidic protein (GFAP), calcium-binding protein (S100B), and neuron-specific enolase (NSE) are brain damage markers. The main goal of this study is to investigate the expression of these markers in the striatum (ST) of chronic/progressive mouse model of PD, and to study the effect of endurance exercise training on the expression of those markers. In this study, forty C57BL/6 albino mice were randomly divided into four groups. Sedentary control (SC, n=10), exercise control (ExC, n=10), sedentary Parkinson's (SPD, n=10), and exercised Parkinson's (ExPD, n=10). Chronic Parkinsonism was induced by injecting the animals with 10 doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg) and probenecid (250 mg/kg) over 5 weeks. Modified human treadmill was used to train the mice at a speed of 18 m/min, 0 degrees of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we examined the expression of these markers on the striatum of the four animal groups using immunohistochemistry. Parkinsonism increases the expression of NSE, S100B, and GFAP in the ST, p value P < 0.001, < 0.05, and < 0.7 respectively compared with control group. Exercise training decreases the expression of NSE, S100B, and GFAP in the exercised PD mice compared with sedentary PD mice p value < 0.005, < 0.02, and < 0.40 respectively. Treadmill exercise training decreased the expression of brain damage markers in the striatum of chronic Parkinsonian mice, which can partially explain the beneficial neuroprotective role of exercise in patients with PD.

Serum homocysteine and physical exercise in patients with Parkinson's disease

Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls. Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey's post hoc test were applied to compare and to verify differences between groups. Pearson's correlation and stepwise multiple regression analyses were used to consider the association between several variables. Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P= 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P= 0.001). A positive relationship between levodopa dose and Hcy concentrations (R(2) = 0.27; P= 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R(2) = 0.023; P= 0.15). The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.

Design and baseline characteristics of the ParkFit study, a randomized controlled trial evaluating the effectiveness of a multifaceted behavioral program to increase physical activity in Parkinson patients

BackgroundMany patients with Parkinson's disease (PD) lead a sedentary lifestyle. Promotion of physical activities may beneficially affect the clinical presentation of PD, and perhaps even modify the course of PD. However, because of physical and cognitive impairments, patients with PD require specific support to increase their level of physical activity.MethodsWe developed the ParkFit Program: a PD-specific and multifaceted behavioral program to promote physical activity. The emphasis is on creating a behavioral change, using a combination of accepted behavioral motivation techniques. In addition, we designed a multicentre randomized clinical trial to investigate whether this ParkFit Program increases physical activity levels over two years in sedentary PD patients. We intended to include 700 sedentary patients. Primary endpoint is the time spent on physical activities per week, which will be measured every six months using an interview-based 7-day recall.ResultsIn total 3453 PD patients were invited to participate. Ultimately, 586 patients - with a mean (SD) age of 64.1 (7.6) years and disease duration of 5.3 (4.5) years - entered the study. Study participants were younger, had a shorter disease duration and were less sedentary compared with eligible PD patients not willing to participate.DiscussionThe ParkFit trial is expected to yield important new evidence about behavioral interventions to promote physical activity in sedentary patients with PD. The results of the trial are expected in 2012.Trial registrationhttp://clinicaltrials.gov (nr NCT00748488).