AMPK agonist AICAR delays the initial decline in lifetime-apex V̇o2 peak, while voluntary wheel running fails to delay its initial decline in female rats

2016 ◽  
Vol 48 (2) ◽  
pp. 101-115 ◽  
Author(s):  
Ryan G. Toedebusch ◽  
Gregory N. Ruegsegger ◽  
Joshua F. Braselton ◽  
Alexander J. Heese ◽  
John C. Hofheins ◽  
...  
Keyword(s):  
Protein Concentration ◽  
Molecular Mechanisms ◽  
Outcome Measure ◽  
Wheel Running ◽  
Female Rats ◽  
Peak Oxygen Consumption ◽  
Chronological Age ◽  
Primary Hypothesis ◽  
Running Wheels ◽  
Voluntary Wheel

There has never been an outcome measure for human health more important than peak oxygen consumption (V̇o2 peak), yet little is known regarding the molecular triggers for its lifetime decline with aging. We examined the ability of physical activity or 5 wk of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) administration to delay the initial aging-induced decline in lifetime-apex V̇o2 peak and potential underlying molecular mechanisms. Experiment 1 consisted of female rats with (RUN) and without (NO RUN) running wheels, while experiment 2 consisted of female nonrunning rats getting the AMPK agonist AICAR (0.5 mg/g/day) subcutaneously for 5 wk beginning at 17 wk of age. All rats underwent frequent, weekly or biweekly V̇o2 peak tests beginning at 10 wk of age. In experiment 1, lifetime-apex V̇o2 peak occurred at 19 wk of age in both RUN and NO RUN and decreased thereafter. V̇o2 peak measured across experiment 1 was ∼25% higher in RUN than in NO RUN. In experiment 2, AICAR delayed the chronological age observed in experiment 1 by 1 wk, from 19 wk to 20 wk of age. RUN and NO RUN showed different skeletal muscle transcriptomic profiles both pre- and postapex. Additionally, growth and development pathways are differentially regulated between RUN and NO RUN. Angiomotin mRNA was downregulated postapex in RUN and NO RUN. Furthermore, strong significant correlations to V̇o2 peak and trends for decreased protein concentration supports angiomotin's potential importance in our model. Contrary to our primary hypothesis, wheel running was not sufficient to delay the chronological age of lifetime-apex V̇o2 peak decline, whereas AICAR delayed it 1 wk.

scholarly journals Cardiorespiratory fitness through the early lifecourse and attempts to modulate its initial decline

2015 ◽  
Author(s):  
◽  
Ryan Toedebusch
Keyword(s):  
Molecular Mechanisms ◽  
Wheel Running ◽  
Human Life ◽  
Strong Predictor ◽  
Transcriptomic Analysis ◽  
Female Rats ◽  
Chronological Age ◽  
Two Phases ◽  
Running Wheels ◽  
Muscle Gene

There has never been an outcome measure for human health more important than VO2peak, yet we know nothing about the molecular triggers for its decline with aging. Peak aerobic capacity (VO2peak) is a strong predictor of morbidity and mortality. Lifetime-apex VO2peak is the highest value for VO2peak during the life course and declines beginning the 3rd decade of human life. I examined the ability of chronic voluntary wheel running, or 5-weeks of AICAR administration, to delay the chronological age at which the decline of lifetime-apex VO2peak begins and potential underlying molecular mechanisms. Experiment one consisted of female rats with (RUN) and without (NO RUN) running wheels that underwent frequent VO2peak tests beginning at 10-weeks of age and continuing until 27-weeks of age. Lifetime apex-VO2peak occurred at 19 weeks of age in both groups, decreasing thereafter. On average, VO2peak measured across experiment one was [about]25% higher in RUN. Experiment two used the AMPK-agonist AICAR, beginning at 17-weeks of age to test if the chronological age for lifetime-apex VO2peak decline could be shifted to an older age. Two groups of female rats, AICAR (0.5 mg/kg daily) and vehicle (VEH, saline) were used for 5-weeks and all animals were sacrificed at 22-weeks of age. Compared to VEH group, AICAR rats showed significantly higher body weights, muscle weights, heart weights and lower % body fat. Additionally, AICAR was able to delay the initial decline by one-week, from 19- to 20-weeks of age, but was lowered to VEH levels at 22- weeks of age. Transcriptomic analysis of the lateral head of the tricep muscle from experiment one animals revealed mRNA differences in RUN vs. NO RUN, suggesting differing skeletal muscle gene regulation immediately prior to lifetime-apex VO2peak decline. Two phases of life were examined, pre-apex VO2peak (17- to 19-weeks of age) and post-apex (19- to 27-weeks of age). These data indicate that rat wheel running increases VO2peak 25% and is not sufficient to delay the chronological age of lifetime-apex VO2peak decline, whereas AICAR delayed it one week. Transcriptomic analysis of experiment one offers target molecules that play a role in: 1) the causation of the decline occurring at 19-weeks of age, and 2) potential genes and mechanisms contributing to the initiation of decline in lifetime-apex VO2peak.

scholarly journals Voluntary exercise and depression-like behavior in rodents: are we running in the right direction?

2018 ◽  
Vol 60 (3) ◽  
pp. R77-R95 ◽  
Author(s):  
Joram D Mul
Keyword(s):  
Exercise Training ◽  
Molecular Mechanisms ◽  
Wheel Running ◽  
Financial Burden ◽  
Modern Society ◽  
Mental Illnesses ◽  
Voluntary Exercise ◽  
Voluntary Wheel Running ◽  
Beneficial Effects ◽  
Voluntary Wheel

Acute or chronic exposure to stress can increase the risk to develop major depressive disorder, a severe, recurrent and common psychiatric condition. Depression places an enormous social and financial burden on modern society. Although many depressed patients are treated with antidepressants, their efficacy is only modest, underscoring the necessity to develop clinically effective pharmaceutical or behavioral treatments. Exercise training produces beneficial effects on stress-related mental disorders, indicative of clinical potential. The pro-resilient and antidepressant effects of exercise training have been documented for several decades. Nonetheless, the underlying molecular mechanisms and the brain circuitries involved remain poorly understood. Preclinical investigations using voluntary wheel running, a frequently used rodent model that mimics aspects of human exercise training, have started to shed light on the molecular adaptations, signaling pathways and brain nuclei underlying the beneficial effects of exercise training on stress-related behavior. In this review, I highlight several neurotransmitter systems that are putative mediators of the beneficial effects of exercise training on mental health, and review recent rodent studies that utilized voluntary wheel running to promote our understanding of exercise training-induced central adaptations. Advancements in our mechanistic understanding of how exercise training induces beneficial neuronal adaptations will provide a framework for the development of new strategies to treat stress-associated mental illnesses.

scholarly journals Physical Activity Dynamically Regulates the Hippocampal Proteome along the Dorso-Ventral Axis

2020 ◽  
Vol 21 (10) ◽  
pp. 3501
Author(s):  
Surina Frey ◽  
Rico Schieweck ◽  
Ignasi Forné ◽  
Axel Imhof ◽  
Tobias Straub ◽  
...  
Keyword(s):  
Physical Activity ◽  
Regional Differences ◽  
Molecular Mechanisms ◽  
Wheel Running ◽  
Actin Binding ◽  
Label Free ◽  
Therapeutic Approaches ◽  
Cytoskeleton Remodeling ◽  
Insight Into ◽  
Voluntary Wheel

The hippocampus is central for higher cognition and emotions. In patients suffering from neuropsychiatric or neurodegenerative diseases, hippocampal signaling is altered causing cognitive defects. Thus, therapeutic approaches aim at improving cognition by targeting the hippocampus. Enhanced physical activity (EPA) improves cognition in rodents and humans. A systematic screen, however, for expression changes in the hippocampus along the dorso-ventral axis is missing, which is a prerequisite for understanding molecular mechanisms. Here, we exploited label free mass spectrometry to detect proteomic changes in the hippocampus of male mice upon voluntary wheel running. To identify regional differences, we examined dorsal and ventral CA1, CA3 and dentate gyrus hippocampal subregions. We found metabolic enzymes and actin binding proteins, such as RhoA, being upregulated in the hippocampus upon EPA suggesting a coordination between metabolism and cytoskeleton remodeling; two pathways essential for synaptic plasticity. Strikingly, dorsal and ventral hippocampal subregions respond differentially to EPA. Together, our results provide new insight into proteomic adaptations driven by physical activity in mice. In addition, our results suggest that dorsal and ventral hippocampus, as well as hippocampal subregions themselves, contribute differently to this process. Our study therefore provides an important resource for studying hippocampal subregion diversity in response to EPA.

Voluntary wheel running effects on intra-accumbens opioid driven diet preferences in male and female rats

2019 ◽  
Vol 155 ◽  
pp. 22-30
Author(s):  
Jenna R. Lee ◽  
Melissa A. Tapia ◽  
Valerie N. Weise ◽  
Emily L. Bathe ◽  
Victoria J. Vieira-Potter ◽  
...  
Keyword(s):  
Wheel Running ◽  
Female Rats ◽  
Voluntary Wheel Running ◽  
Male And Female ◽  
Male And Female Rats ◽  
Voluntary Wheel ◽  
Diet Preferences

scholarly journals Comparison of changes in electrical activity, in isolated and in vivo hearts, induced by voluntary exercise in female rats

2020 ◽  
Author(s):  
Rachel Stones ◽  
Mark Drinkhill ◽  
Ed White
Keyword(s):  
Exercise Training ◽  
Electrical Activity ◽  
Wheel Running ◽  
Left Ventricular ◽  
Voluntary Exercise ◽  
Female Rats ◽  
Heart Weight ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

AbstractRegular mild exercise is recommended to the general population as beneficial to health. Regular exercise typically leads to structural and electrical remodelling of the heart but in human studies it is difficult to relate the extrinsic and intrinsic influences on intact hearts to changes seen at the single cell level. In this study we wished to test whether changes in electrical activity in intact hearts, in response to voluntary wheel running exercise training, were consistent with our previous observations in single cardiac myocytes and whether these changes resulted in altered susceptibility to arrhythmic stimuli.Female rats performed 5 weeks of voluntary wheel running. Implanted telemetry transmitters were used to measure electrocardiograms (ECGs) and determine heart rate variability (HRV) in conscious, unrestrained, trained (TRN) and sedentary (SED) animals. In isolated hearts, left ventricular epicardial monophasic action potentials (MAPs) were recorded and the responses to potentially arrhythmic interventions were assessed.Exercise training caused cardiac hypertrophy, as indexed by a significantly greater heart weight to body weight ratio. Consistent with previous measurements of action potential duration in single myocytes, MAPs were significantly longer at 50%, 75% and 90% repolarization. Arrhythmic susceptibility was not different between SED and TRN hearts. Trained animals displayed significantly altered HRV by week 5, in a manner consistent with reduced sympathetic tone, however resting ECG parameters, including those most associated with repolarisation duration, were unaltered. We conclude that intrinsic changes to cellular cardiac electrophysiology, induced by mild voluntary exercise, are not attenuated by the electronic loading that occurs in intact hearts. However, in vivo, extrinsic neuro-hormonal control of the heart may minimize the effects of intrinsic alterations in electrical activity.

Effects of Voluntary Wheel Running on Cardiac Function in Female Rats Receiving Chemical Ovariectomy

2007 ◽  
Vol 39 (Supplement) ◽  
pp. S53
Author(s):  
David S. Hydock ◽  
Chia-Ying Lien ◽  
Carole M. Schneider ◽  
Reid Hayward
Keyword(s):  
Cardiac Function ◽  
Wheel Running ◽  
Female Rats ◽  
Voluntary Wheel Running ◽  
Voluntary Wheel

Effects of Goserelin Acetate and Voluntary Wheel Running on Bone Morphology in Female Rats

2008 ◽  
Vol 40 (Supplement) ◽  
pp. S82
Author(s):  
Traci Parry ◽  
David S. Hydock ◽  
Urszula T. Iwaniec ◽  
Russell T. Turner ◽  
Chia-Ying Lien ◽  
...  
Keyword(s):  
Wheel Running ◽  
Female Rats ◽  
Bone Morphology ◽  
Voluntary Wheel Running ◽  
Goserelin Acetate ◽  
Voluntary Wheel

Glucose transporters and maximal transport are increased in endurance-trained rat soleus

1992 ◽  
Vol 73 (2) ◽  
pp. 486-492 ◽  
Author(s):  
C. A. Slentz ◽  
E. A. Gulve ◽  
K. J. Rodnick ◽  
E. J. Henriksen ◽  
J. H. Youn ◽  
...  
Keyword(s):  
Training Program ◽  
Glucose Transport ◽  
Soleus Muscle ◽  
Protein Concentration ◽  
Citrate Synthase ◽  
Wheel Running ◽  
Contractile Activity ◽  
Treadmill Running ◽  
Female Rats ◽  
Transport Activity

Voluntary wheel running induces an increase in the concentration of the regulatable glucose transporter (GLUT4) in rat plantaris muscle but not in soleus muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425–1429, 1990). Wheel running also causes hypertrophy of the soleus in rats. This study was undertaken to ascertain whether endurance training that induces enzymatic adaptations but no hypertrophy results in an increase in the concentration of GLUT4 protein in rat soleus (slow-twitch red) muscle and, if it does, to determine whether there is a concomitant increase in maximal glucose transport activity. Female rats were trained by treadmill running at 25 m/min up a 15% grade, 90 min/day, 6 days/wk for 3 wk. This training program induced increases of 52% in citrate synthase activity, 66% in hexokinase activity, and 47% in immunoreactive GLUT4 protein concentration in soleus muscles without causing hypertrophy. Glucose transport activity stimulated maximally with insulin plus contractile activity was increased to roughly the same extent (44%) as GLUT4 protein content in soleus muscle by the treadmill exercise training. In a second set of experiments, we examined whether a swim-training program increases glucose transport activity in the soleus in the presence of a maximally effective concentration of insulin. The swimming program induced a 44% increase in immunoreactive GLUT4 protein concentration. Glucose transport activity maximally stimulated with insulin was 62% greater in soleus muscle of the swimmers than in untrained controls. Training did not alter the basal rate of 2-deoxyglucose uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

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