(136) Voluntary wheel running can improve increased urogenital sensitivity and function resulting from neonatal maternal separation in male mice

Selective breeding is an important tool in behavioral genetics and evolutionary physiology, but it has rarely been applied to the study of exercise physiology. We are using artificial selection for increased wheel-running behavior to study the correlated evolution of locomotor activity and physiological determinants of exercise capacity in house mice. We studied enzyme activities and their response to voluntary wheel running in mixed hindlimb muscles of mice from generation 14, at which time individuals from selected lines ran more than twice as many revolutions per day as those from control (unselected) lines. Beginning at weaning and for 8 wk, we housed mice from each of four replicate selected lines and four replicate control lines with access to wheels that were free to rotate (wheel-access group) or locked (sedentary group). Among sedentary animals, mice from selected lines did not exhibit a general increase in aerobic capacities: no mitochondrial [except pyruvate dehydrogenase (PDH)] or glycolytic enzyme activity was significantly ( P < 0.05) higher than in control mice. Sedentary mice from the selected lines exhibited a trend for higher muscle aerobic capacities, as indicated by higher levels of mitochondrial (cytochrome- c oxidase, carnitine palmitoyltransferase, citrate synthase, and PDH) and glycolytic (hexokinase and phosphofructokinase) enzymes, with concomitant lower anaerobic capacities, as indicated by lactate dehydrogenase (especially in male mice). Consistent with previous studies of endurance training in rats via voluntary wheel running or forced treadmill exercise, cytochrome- c oxidase, citrate synthase, and carnitine palmitoyltransferase activity increased in the wheel-access groups for both genders; hexokinase also increased in both genders. Some enzymes showed gender-specific responses: PDH and lactate dehydrogenase increased in wheel-access male but not female mice, and glycogen phosphorylase decreased in female but not in male mice. Two-way analysis of covariance revealed significant interactions between line type and activity group; for several enzymes, activities showed greater changes in mice from selected lines, presumably because such mice ran more revolutions per day and at greater velocities. Thus genetic selection for increased voluntary wheel running did not reduce the capability of muscle aerobic capacity to respond to training.

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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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Treadmill Training Improves Aerobic Capacity in Aged Male Mice Compared to Voluntary Wheel Running

Innovation in Aging ◽

10.1093/geroni/igab046.2565 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 688-688

Author(s):

Emily Schmitt ◽

Hunter Graves ◽

Danielle Bruns

Keyword(s):

Aerobic Capacity ◽

Wheel Running ◽

Treadmill Training ◽

Treadmill Running ◽

Time To Exhaustion ◽

Male Mice ◽

Voluntary Wheel Running ◽

Age Related ◽

Training Protocol ◽

Voluntary Wheel

Abstract Preclinical exercise studies typically use two forms of exercise training protocols: 1) voluntary wheel running and 2) forced treadmill running. Previous work from our group clearly demonstrates that older (18-month-old) male mice do not voluntarily engage in wheel running, especially compared to younger males or female mice. Therefore, we implemented a forced exercise treadmill training protocol to determine if treadmill training was superior to wheel running in improving aerobic capacity in older male mice. Purpose To determine if a 3-week treadmill training protocol improved time to exhaustion (TTE) in older male mice. Methods 18-month-old male mice (n=5) were provided a running wheel in their individual cage for 2 weeks or underwent daily treadmill training (n=6) for 3 weeks with increasing speed/incline. At the end of the training period we assessed TTE. Results Older male mice that trained on the treadmill demonstrated higher TTE compared to wheel (1382 □ 32 seconds versus 500 □ 99 seconds, respectively). In addition, older male mice that trained on the treadmill improved on average ~8% in their TTE test. Conclusion A 3-week treadmill training protocol improves aerobic capacity in older male mice to a greater extent than voluntary wheel running. Ongoing experiments will utilize this training protocol to understand age-related declines in cardiorespiratory fitness, circadian rhythm, and to test exercise as an intervention in the aging population.

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