Comparative adaptations in oxidative and glycolytic muscle fibers in a low voluntary wheel running rat model performing three levels of physical activity

AbstractChronic kidney disease (CKD) leads to musculoskeletal impairments that are impacted by muscle metabolism. We tested the hypothesis that 10-weeks of voluntary wheel running can improve skeletal muscle mitochondria activity and function in a rat model of CKD. Groups included (n = 12–14/group): (1) normal littermates (NL); (2) CKD, and; (3) CKD-10 weeks of voluntary wheel running (CKD-W). At 35-weeks old the following assays were performed in the soleus and extensor digitorum longus (EDL): targeted metabolomics, mitochondrial respiration, and protein expression. Amino acid-related compounds were reduced in CKD muscle and not restored by physical activity. Mitochondrial respiration in the CKD soleus was increased compared to NL, but not impacted by physical activity. The EDL respiration was not different between NL and CKD, but increased in CKD-wheel rats compared to CKD and NL groups. Our results demonstrate that the soleus may be more susceptible to CKD-induced changes of mitochondrial complex content and respiration, while in the EDL, these alterations were in response the physiological load induced by mild physical activity. Future studies should focus on therapies to improve mitochondrial function in both types of muscle to determine if such treatments can improve the ability to adapt to physical activity in CKD.

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Circadian pattern of total and free corticosterone concentrations, corticosteroid-binding globulin, and physical activity in mice selectively bred for high voluntary wheel-running behavior

General and Comparative Endocrinology ◽

10.1016/j.ygcen.2008.01.020 ◽

2008 ◽

Vol 156 (2) ◽

pp. 210-217 ◽

Cited By ~ 87

Author(s):

Jessica L. Malisch ◽

Creagh W. Breuner ◽

Fernando R. Gomes ◽

Mark A. Chappell ◽

Theodore Garland

Keyword(s):

Physical Activity ◽

Wheel Running ◽

Circadian Pattern ◽

Voluntary Wheel Running ◽

Corticosteroid Binding Globulin ◽

Voluntary Wheel

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Voluntary wheel running ameliorates vascular smooth muscle hyper-contractility in type 2 diabetic db/db mice

Applied Physiology Nutrition and Metabolism ◽

10.1139/h07-058 ◽

2007 ◽

Vol 32 (4) ◽

pp. 711-720 ◽

Cited By ~ 9

Author(s):

Karyn A. Esser ◽

Wen Su ◽

Sergey Matveev ◽

Vicki Wong ◽

Li Zeng ◽

...

Keyword(s):

Physical Activity ◽

Smooth Muscle ◽

Blood Glucose ◽

Vascular Smooth Muscle ◽

Wheel Running ◽

Voluntary Wheel Running ◽

Voluntary Physical Activity ◽

Type 2 Diabetic ◽

Voluntary Wheel

Physical activity reduces cardiovascular disease related mortality in diabetic patients. However, it is unknown if the diabetic state reduces voluntary physical activity and, if so, if the voluntary physical activity at the reduced level is sufficient to improve cardiovascular risk factors. To address these two specific questions, we investigated voluntary wheel running performance in an obese and type 2 diabetic mouse model, the db/db mice. In addition, we determined the effects of running on body mass, blood glucose, insulin, plasma free fatty acids, cholesterol, and vascular smooth muscle hyper-contractility. Our results showed that daily running distance, time, and speed were significantly reduced in the db/db mice to about 23%, 32%, and 71%, respectively, of that in non-diabetic control mice. However, this low level of running was sufficient to induce a reduction in the vascular smooth muscle hyper-contractility, cholesterol, and some plasma free fatty acids, as well as to delay the decrease in blood insulin. These changes occurred in the absence of weight loss and a detectable decrease in blood glucose. Thus, the results of this study demonstrated that voluntary wheel running activity was dramatically reduced in db/db mice. However, the low levels of running were beneficial, in the absence of effects on obesity or blood glucose, with significant reductions in cardiovascular risk factors and potential delays in β-cell dysfunction.

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Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice

10.1101/2020.04.24.060608 ◽

2020 ◽

Author(s):

Rachel P. Tillage ◽

Genevieve E. Wilson ◽

L. Cameron Liles ◽

Philip V. Holmes ◽

David Weinshenker

Keyword(s):

Physical Activity ◽

Locus Coeruleus ◽

Wheel Running ◽

Neuropsychiatric Disorders ◽

Noradrenergic Neurons ◽

Stress Resilience ◽

Voluntary Wheel Running ◽

Exercise Induced ◽

Species Specific ◽

Voluntary Wheel

ABSTRACTThe neuropeptide galanin has been implicated in stress-related neuropsychiatric disorders in both humans and rodent models. While pharmacological treatments for these disorders are ineffective for many individuals, physical activity is beneficial for stress-related symptoms. Galanin is highly expressed in the noradrenergic system, particularly the locus coeruleus (LC), which is dysregulated in stress-related disorders and activated by exercise. Galanin expression is elevated in the LC by chronic exercise, and blockade of galanin transmission attenuates exercise-induced stress resilience. However, most research on this topic has been done in rats, so it is unclear whether the relationship between exercise and galanin is species-specific. Moreover, use of intracerebroventricular galanin receptor antagonists in prior studies precluded defining a causal role for LC-derived galanin specifically. Therefore, the goals of this study were twofold. First, we investigated whether physical activity (chronic voluntary wheel running) increases stress resilience and galanin expression in the LC of mice. Next, we used transgenic mice that overexpress galanin in noradrenergic neurons (Gal OX) to determine how chronically elevated noradrenergic-derived galanin, alone, alters anxiogenic-like responses to stress. We found that three weeks of ad libitum access to a running wheel in their home cage increased galanin mRNA in the LC of mice and conferred resilience to a stressor. The effects of exercise were phenocopied by galanin overexpression in noradrenergic neurons, and Gal OX mice were resistant to the anxiogenic effect of optogenetic LC activation. Together, these findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.Significance statementUnderstanding the neurobiological mechanisms underlying behavioral responses to stress is necessary to improve treatments for stress-related neuropsychiatric disorders. Increased physical activity is associated with stress resilience in humans, but the neurobiological mechanisms underlying this effect are not clear. Here we investigate the anxiolytic potential of the neuropeptide galanin from the main noradrenergic nucleus, the locus coeruleus (LC). We show that chronic voluntary wheel running in mice galanin expression in the LC and stress resilience. Furthermore, we show that genetic overexpression of galanin in noradrenergic neurons confers resilience to the anxiogenic effects of foot shock and optogenetic LC activation. These findings support a role for chronically increased noradrenergic galanin in mediating resilience to stress.

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Impaired Voluntary Wheel Running Behavior in the Unilateral 6-Hydroxydopamine Rat Model of Parkinson's Disease

Journal of Korean Neurosurgical Society ◽

10.3340/jkns.2015.57.2.82 ◽

2015 ◽

Vol 57 (2) ◽

pp. 82 ◽

Cited By ~ 5

Author(s):

Qi Pan ◽

Wangming Zhang ◽

Jinyan Wang ◽

Fei Luo ◽

Jingyu Chang ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Rat Model ◽

Wheel Running ◽

Voluntary Wheel Running ◽

6 Hydroxydopamine ◽

Voluntary Wheel

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Sex dependent effects of physical activity on diet preference in rats selectively bred for high or low levels of voluntary wheel running

Behavioural Brain Research ◽

10.1016/j.bbr.2018.10.018 ◽

2019 ◽

Vol 359 ◽

pp. 95-103 ◽

Cited By ~ 8

Author(s):

Jenna R. Lee ◽

Melissa A. Tapia ◽

Jane R. Nelson ◽

Justin M. Moore ◽

Graydon B. Gereau ◽

...

Keyword(s):

Physical Activity ◽

Wheel Running ◽

Voluntary Wheel Running ◽

Diet Preference ◽

Low Levels ◽

Voluntary Wheel

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Interrelationship of CB1R and OBR pathways in regulation of metabolic, neuroendocrine, and behavioral responses to food restriction and voluntary wheel running

Journal of Applied Physiology ◽

10.1152/japplphysiol.01303.2013 ◽

2014 ◽

Vol 117 (2) ◽

pp. 97-104 ◽

Cited By ~ 3

Author(s):

Abdoulaye Diane ◽

Donna F. Vine ◽

James C. Russell ◽

C. Donald Heth ◽

W. David Pierce ◽

...

Keyword(s):

Physical Activity ◽

Body Weight ◽

Food Restriction ◽

Leptin Receptor ◽

Wheel Running ◽

Behavioral Responses ◽

Voluntary Wheel Running ◽

Cannabinoid 1 Receptor ◽

Clinical Measures ◽

Voluntary Wheel

We hypothesized the cannabinoid-1 receptor and leptin receptor (ObR) operate synergistically to modulate metabolic, neuroendocrine, and behavioral responses of animals exposed to a survival challenge (food restriction and wheel running). Obese-prone (OP) JCR:LA- cp rats, lacking functional ObR, and lean-prone (LP) JCR:LA- cp rats (intact ObR) were assigned to OP-C and LP-C (control) or CBR1-antagonized (SR141716, 10 mg/kg body wt in food) OP-A and LP-A groups. After 32 days, all rats were exposed to 1.5-h daily meals without the drug and 22.5-h voluntary wheel running, a survival challenge that normally culminates in activity-based anorexia (ABA). Rats were removed from the ABA protocol when body weight reached 75% of entry weight (starvation criterion) or after 14 days (survival criterion). LP-A rats starved faster (6.44 ± 0.24 days) than LP-C animals (8.00 ± 0.29 days); all OP rats survived the ABA challenge. LP-A rats lost weight faster than animals in all other groups ( P < 0.001). Consistent with the starvation results, LP-A rats increased the rate of wheel running more rapidly than LP-C rats ( P = 0.001), with no difference in hypothalamic and primary neural reward serotonin levels. In contrast, OP-A rats showed suppression of wheel running compared with the OP-C group ( days 6–14 of ABA challenge, P < 0.001) and decreased hypothalamic and neural reward serotonin levels ( P < 0.01). Thus there is an interrelationship between cannabinoid-1 receptor and ObR pathways in regulation of energy balance and physical activity. Effective clinical measures to prevent and treat a variety of disorders will require understanding of the mechanisms underlying these effects.

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P4475Vasodilation- and blood pressure normalization-independent cardioprotective effects of endogenous, physical activity-induced alpha calcitonin gene-related peptide in chronic hypertension

European Heart Journal ◽

10.1093/eurheartj/ehz745.0870 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T Skaria ◽

K Mitchell ◽

J A Fischer ◽

W Born ◽

M Gassmann ◽

...

Keyword(s):

Physical Activity ◽

Blood Pressure ◽

Cardiac Tissue ◽

Wheel Running ◽

Chronic Hypertension ◽

Voluntary Wheel Running ◽

Cardioprotective Effects ◽

Pressure Independent ◽

And Function ◽

Voluntary Wheel

Abstract Background Alpha calcitonin gene-related peptide (αCGRP) is one of the strongest vasodilators and, as such, is cardioprotective in chronic hypertension when reducing the associated elevated blood pressure. However, we hypothesize that endogenous, physical activity-induced αCGRP has blood pressure independent cardioprotective effects in chronic hypertension. Methods Chronic hypertension was induced in WT and αCGRP−/− mice by one-kidney one-clip surgery. Chronic hypertensive WT and αCGRP−/− mice lived sedentarily or performed voluntary wheel running and were treated simultaneously with either vehicle, αCGRP or αCGRP receptor antagonist CGRP8–37. Cardiac function and tissue phenotype were evaluated echocardiographically and by ddPCR, Western blotting and histology, respectively. Results Blood pressure was similar among all hypertensive experimental groups. Endogenous αCGRP limited pathological cardiac remodeling and symptomatic heart failure already in sedentary, chronic hypertensive WT mice. In these mice, voluntary wheel running significantly improved cardiac tissue phenotype and function, that was abolished by CGRP8–37 treatment. In αCGRP−/− mice, αCGRP treatment, in contrast to voluntary wheel running, improved cardiac tissue phenotype and function. Specific inhibition of proliferation and myofibroblast differentiation of primary murine cardiac fibroblasts by αCGRP suggests involvement of these cells in αCGRP-mediated blunting of pathological cardiac remodeling. Conclusion Endogenous, physical activity-induced αCGRP has blood pressure independent cardioprotective effects and is crucial for maintaining cardiac function in chronic hypertension. Consequently, permanently inhibiting endogenous αCGRP signaling, as currently approved for migraine prophylaxis, could endanger hypertensive patients. Acknowledgement/Funding Swiss National Science Foundation, Novartis Foundation for Medical-biological Research

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Hippocampal Morphology in a Rat Model of Depression: The Effects of Physical Activity

The Open Neuroimaging Journal ◽

10.2174/1874440001509010001 ◽

2015 ◽

Vol 9 (1) ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Adam Sierakowiak ◽

Anna Mattsson ◽

Marta Gómez-Galán ◽

Teresa Feminía ◽

Lisette Graae ◽

...

Keyword(s):

Physical Activity ◽

Genetic Model ◽

Wheel Running ◽

Ex Vivo ◽

Hippocampal Volume ◽

Antidepressant Effect ◽

Spine Density ◽

Voluntary Wheel Running ◽

Voluntary Wheel

Accumulating in vivo and ex vivo evidences show that humans suffering from depression have decreased hippocampal volume and altered spine density. Moreover, physical activity has an antidepressant effect in humans and in animal models, but to what extent physical activity can affect hippocampal volume and spine numbers in a model for depression is not known. In this study we analyzed whether physical activity affects hippocampal volume and spine density by analyzing a rodent genetic model of depression, Flinders Sensitive Line Rats (FSL), with Magnetic Resonance Imaging (MRI) and ex vivo Golgi staining. We found that physical activity in the form of voluntary wheel running during 5 weeks increased hippocampal volume. Moreover, runners also had larger numbers of thin spines in the dentate gyrus. Our findings support that voluntary wheel running, which is antidepressive in FSL rats, is associated with increased hippocampal volume and spine numbers.

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Voluntary Wheel Running Has Beneficial Effects in a Rat Model of CKD-Mineral Bone Disorder (CKD-MBD)

Journal of the American Society of Nephrology ◽

10.1681/asn.2019040349 ◽

2019 ◽

Vol 30 (10) ◽

pp. 1898-1909 ◽

Cited By ~ 1

Author(s):

Keith G. Avin ◽

Matthew R. Allen ◽

Neal X. Chen ◽

Shruthi Srinivasan ◽

Kalisha D. O’Neill ◽

...

Keyword(s):

Kidney Disease ◽

Rat Model ◽

Wheel Running ◽

Serum Biochemistry ◽

Left Ventricular ◽

Cystic Kidney Disease ◽

Cystic Kidney ◽

Voluntary Wheel Running ◽

Exercise Interventions ◽

Voluntary Wheel

BackgroundReduced bone and muscle health in individuals with CKD contributes to their higher rates of morbidity and mortality.MethodsWe tested the hypothesis that voluntary wheel running would improve musculoskeletal health in a CKD rat model. Rats with spontaneous progressive cystic kidney disease (Cy/+ IU) and normal littermates (NL) were given access to a voluntary running wheel or standard cage conditions for 10 weeks starting at 25 weeks of age when the rats with kidney disease had reached stage 2–3 of CKD. We then measured the effects of wheel running on serum biochemistry, tissue weight, voluntary grip strength, maximal aerobic capacity (VO2max), body composition and bone micro-CT and mechanics.ResultsWheel running improved serum biochemistry with decreased creatinine, phosphorous, and parathyroid hormone in the rats with CKD. It improved muscle strength, increased time-to-fatigue (for VO2max), reduced cortical porosity and improved bone microarchitecture. The CKD rats with voluntary wheel access also had reduced kidney cystic weight and reduced left ventricular mass index.ConclusionsVoluntary wheel running resulted in multiple beneficial systemic effects in rats with CKD and improved their physical function. Studies examining exercise interventions in patients with CKD are warranted.

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