Exercise Cages Research Articles

Effect of aging and exercise on hTERT expression in thymus tissue of hTERT transgenic bacterial artificial chromosome mice.

Telomere shortening occurs with aging in immune cells and may be related to immunosenescence. Exercise can upregulate telomerase activity and attenuate telomere shortening in immune cells, but it is unknown if exercise impacts other immune tissues such as the thymus. This study aimed to examine human telomerase reverse transcriptase (hTERT) alternative splicing (AS) in response to aging and exercise in thymus tissue. Transgenic mice with a human TERT bacterial artificial chromosome integrated into its genome (hTERT-BAC) were utilized in two different exercise models. Mice of different ages were assigned to an exercise cage (running wheel) or not for 3weeks prior to thymus tissue excision. Middle-aged mice (16months) were exposed or not to treadmill running (30min at 60% maximum speed) prior to thymus collection. hTERT transcript variants were measured by RT-PCR. hTERT transcripts decreased with aging (r = - 0.7511, p < 0.0001) and 3weeks of wheel running did not counteract this reduction. The ratio of exons 7/8 containing hTERT to total hTERT transcripts increased with aging (r = 0.3669, p = 0.0423) but 3weeks of voluntary wheel running attenuated this aging-driven effect (r = 0.2013, p = 0.4719). Aging increased the expression of senescence marker p16 with no impact of wheel running. Thymus regeneration transcription factor, Foxn1, went down with age with no impact of wheel running exercise. Acute treadmill exercise did not induce any significant changes in thymus hTERT expression or AS variant ratio (p > 0.05). In summary, thymic hTERT expression is reduced with aging. Exercise counteracted a shift in hTERT AS ratio with age. Our data demonstrate that aging impacts telomerase expression and that exercise impacts dysregulated splicing that occurs with aging.

Emergence of functionally aberrant and subsequent reduction of neuromuscular connectivity and improved motor performance after cervical spinal cord injury in Rhesus.

The paralysis that occurs after a spinal cord injury, particularly during the early stages of post-lesion recovery (∼6 weeks), appears to be attributable to the inability to activate motor pools well beyond their motor threshold. In the later stages of recovery, however, the inability to perform a motor task effectively can be attributed to abnormal activation patterns among motor pools, resulting in poor coordination. We have tested this hypothesis on four adult male Rhesus monkeys (Macaca mulatta), ages 6-10 years, by recording the EMG activity levels and patterns of multiple proximal and distal muscles controlling the upper limb of the Rhesus when performing three tasks requiring different levels of skill before and up to 24 weeks after a lateral hemisection at C7. During the recovery period the animals were provided routine daily care, including access to a large exercise cage (5' × 7' × 10') and tested every 3-4 weeks for each of the three motor tasks. At approximately 6-8 weeks the animals were able to begin to step on a treadmill, perform a spring-loaded task with the upper limb, and reaching, grasping, and eating a grape placed on a vertical stick. The predominant changes that occurred, beginning at ∼6-8 weeks of the recovery of these tasks was an elevated level of activation of most motor pools well beyond the pre-lesion level. As the chronic phase progressed there was a slight reduction in the EMG burst amplitudes of some muscles and less incidence of co-contraction of agonists and antagonists, probably contributing to an improved ability to selectively activate motor pools in a more effective temporal pattern. Relative to pre-lesion, however, the EMG patterns even at the initial stages of recovery of successfully performing the different motor tasks, the level of activity of most muscle remained higher. Perhaps the most important concept that emerges from these data is the large combinations of adaptive strategies in the relative level of recruitment and the timing of the peak levels of activation of different motor pools can progressively provide different stages to regain a motor skill.

Maternal exercise improves markers of metabolic signaling and reduces inflammation in brown adipose tissue of offspring

Maternal obesity impacts approximately one-third of pregnant people and impacts offspring through the transmission of obesogenic and diabetic traits. Pregnant patients often spend considerable time sedentary, which has been associated with harmful cardiometabolic changes. Our recent data show that compared with sedentary conditions, voluntary exercise during pregnancy in mice shifts adipose distribution of offspring away from energy storing white adipose tissue towards energy burning brown adipose tissue (BAT), which could improve energy metabolism over the lifespan. The objective of this study was to test the hypothesis that voluntary exercise in pregnant mice improves metabolic signaling pathways and reduces markers of inflammation in BAT from offspring. To test this, female C57BL/6J mice were placed on control diet and allocated to sedentary versus voluntary running wheel exercise cages. Voluntary wheel running was allowed for two weeks prior to breeding and throughout weaning. When offspring were 16 weeks of age, they were euthanized for collection of BAT. The study groups were male sedentary (n=9), female sedentary (n=11), male exercise (n=12), female exercise (n=8). Quantitative real-time polymerase chain reaction was used to measure mRNA of fibroblast-growth factor receptors (β-klotho, Fgfr1, Fgfr2) and inflammation markers (IL10, IL1β, TNFα) in BAT. Outcomes were analyzed by two-way ANOVA to assess effects of exercise, sex, and their interaction. Offspring from exercised mothers had a significant decrease in mRNA of IL1β (1.4±0.4 male sedentary vs. 0.4±0.1 male exercise vs. 1.1±0.2 female sedentary vs. 0.8 ±0.2 female exercise; PSex=0.668, PEX=0.006, PInt=0.098) and TNFα (0.9±0.1 male sedentary vs. 0.5±0.1 male exercise vs. 1.3±0.3 female sedentary vs. 0.6 ±0.1 female exercise; PSex=0.126, PEX=0.007, PInt=0.562) and an increase in Fgfr2 (1.1±0.2 male sedentary vs. 1.7±0.3 male exercise vs. 1.3±0.3 female sedentary vs. 3.8 ±1.2 female exercise; PSex=0.063, PEX=0.011, PInt=0.096) in BAT, which was largely independent of sex. There was no significant main effect of either sex or exercise on IL10, Fgfr1, or β-klotho mRNA in BAT. These data suggest that maternal exercise is associated with decreased inflammation and increased protective metabolic signaling in BAT. This could impact energy metabolism given increasing evidence for advantageous metabolic adaptations with increased BAT health and signaling. Additional studies are needed to further understand the impact of maternal exercise on adipose health, energy metabolism, and cardiovascular outcomes in offspring over the lifespan. American Heart Association Undergraduate Summer Fellowship, Department of Obstetrics and Gynecology at Penn State Milton S Hershey Medical Center, and Dani Peress MD Memorial Fund from the Society of Maternal Fetal Medicine This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Maternal Exercise May Improve Metabolic Outcomes in Offspring in Mice

ObjectiveIt is well recognized in both human epidemiological and animal studies that the maternal in utero environment has significant effects on development of offspring. This includes sedentary lifestyle, which has been linked to developmental programming of metabolic dysfunction. The aim of this study is to investigate metabolic outcomes in offspring of sedentary mice versus mice that exercised in pregnancy.Study DesignC57BL/6J female mice were placed on a control diet and allocated to sedentary versus exercise cages at 17 weeks of age. Exercise cages included a voluntary running wheel, with daily exercise measured via activity trackers. Mice were allowed to exercise for 2 weeks prior to breeding and throughout weaning. Offspring underwent body composition measurement and insulin and glucose tolerance tests at 6 weeks of age. At 14‐16 weeks of age, body composition was reassessed and mice were euthanized for tissue collection. Outcomes were analyzed between sedentary (SED) and exercise (EX) offspring using an unpaired t‐test, with p&lt;0.05 considered significant.ResultsWe studied metabolic function in 10 SED and 9 EX offspring. Insulin sensitivity, measured as the area under the curve for the decrease in glucose over time in response to insulin, tended to be improved in EX versus SED offspring (‐188 vs. 2991; p=0.062), with no difference in fasting glucose levels or glucose tolerance. While body mass was similar at end of study (23.4 EX vs. 23.1 SED; p=0.83), the percentage of subcutaneous white adipose tissue tended to be lower (0.94 EX vs. 1.67 SED; p=0.054) and brown adipose tissue was higher (0.57 EX vs. vs 0.30 SED; p&lt;0.001) in EX offspring.ConclusionsThese data suggest that maternal exercise may improve insulin sensitivity in offspring even under normal diet conditions. Further, despite similar body mass, offspring from mice that exercised during pregnancy had a shift in adipose depot composition with lower white adipose and higher brown adipose tissue. This change in body composition may have important implications for energy metabolism and is an important area of future study.

Physical exercise prevents suppression of hippocampal neurogenesis and reduces cognitive impairment in chemotherapy-treated rats

Chemotherapy, used for the treatment of cancer, often produces cognitive impairment that has been related to suppression of neurogenesis. Physical exercise, which promotes neurogenesis, is known to improve cognitive function in neurologically challenged animals and humans. It is unknown whether exercise similarly protects against chemotherapy-induced cognitive impairment and whether recovery of neurogenesis is a critical factor. The present study investigated the relationship between hippocampal neurogenesis and cognitive performance in chemotherapy-treated rats that engaged in different amounts of physical activity. Groups of rats, housed individually in standard cages or in specially designed cages that allowed unlimited access to a running wheel, received three injections of the chemotherapeutic drugs methotrexate and 5-fluorouracil, or equal volumes of saline. They were then administered the following cognitive tests in a water maze: (1) spatial memory (SM), (2) cued memory, (3) non-matching to sample (NMTS) rule learning; (4) delayed NMTS (DNMTS). Hippocampal neurogenesis was quantified by counting doublecortin-expressing cells in the dentate gyrus. Chemotherapy administered to rats in standard cages resulted in a significant reduction in hippocampal neurogenesis and impaired performance on the SM, NMTS, and DNMTS tasks. In rats receiving chemotherapy and housed in exercise cages, neurogenesis was not suppressed and cognitive performance was similar to controls. Physical exercise can reduce cognitive deficits that result from chemotherapy and this effect is mediated, at least in part, by preventing suppression of drug-induced hippocampal neurogenesis. The results suggest benefits of exercise in preventing or treating cognitive impairment associated with chemotherapy.

The effects of exercise on cocaine self-administration, food-maintained responding, and locomotor activity in female rats: Importance of the temporal relationship between physical activity and initial drug exposure.

Previous studies have reported that exercise decreases cocaine self-administration in rats with long-term access (8+ weeks) to activity wheels in the home cage. The purpose of this study was to (a) examine the importance of the temporal relationship between physical activity and initial drug exposure, (b) determine the effects of exercise on responding maintained by a nondrug reinforcer (i.e., food), and (c) investigate the effects of exercise on cocaine-induced increases in locomotor activity. To this end, female rats were obtained at weaning and divided into 4 groups: (a) EXE-SED rats were housed in exercise cages for 6 weeks and then transferred to sedentary cages after the first day of behavioral testing; (b) SED-EXE rats were housed in sedentary cages for 6 weeks and then transferred to exercise cages after the first day of behavioral testing; (c) SED-SED rats remained in sedentary cages for the duration of the study; and (d) EXE-EXE rats remained in exercise cages for the duration of the study. Relative to the sedentary group (SED-SED), exercise reduced cocaine self-administration in both groups with access to activity wheels after initial drug exposure (EXE-EXE, SED-EXE) but did not reduce cocaine self-administration in the group with access to activity wheels only before drug exposure (EXE-SED). Exercise also decreased the effects of cocaine on locomotor activity but did not reduce responding maintained by food. These data suggest that exercise may reduce cocaine use in drug-experienced individuals with no prior history of aerobic activity without decreasing other types of positively reinforced behaviors.

The effect of housing and environmental enrichment on stereotyped behavior of adult vervet monkeys (Chlorocebus aethiops)

Little information is available on the response of vervet monkeys to different housing conditions or on the suitability of enrichment devices or methods for vervet monkeys. In this study, the authors evaluated the occurrence of stereotyped behavior in adult vervet monkeys under various conditions of housing and enrichment. The variables included cage size, cage level (upper or lower), enrichment with a foraging log, enrichment with an exercise cage and presence of a mate. The authors first determined the incidence of stereotyped behavior in captive-bred, singly housed adult female and male vervet monkeys. They then exposed monkeys to different housing and enrichment situations and compared the incidence of stereotyped behavior among the monkeys. The authors found that more females than males engaged in stereotyped behavior and that females, on average, engaged in such behavior for longer periods of time than males. Stereotyped behavior was most often associated with a small, single cage. The average amount of observed stereotyped activity in monkeys housed in a small cage was significantly lower when the monkeys had access to either a foraging log or an exercise cage. Stereotyped behavior was also lower in female monkeys that were housed (either with a male or without a male) in a larger cage. The least amount of abnormal behavior was associated with the largest, most complex and enriched housing situation. Males and females housed in cages on the lower level of two-level housing engaged in more stereotyped behavior than did monkeys housed in the upper level, regardless of the presence or type of enrichment provided.

Exercise training can attenuate preeclampsia-like features in an animal model

Exercise training benefits have been widely investigated and used as alternative treatment for different pathological conditions. Since preeclampsia is a severe pregnancy-associated disease for which no treatment is available, our aim was to investigate the protective role of exercise training on pregnancy outcome using a mouse model of the disease. We used transgenic female mice overexpressing human angiotensinogen, which develop preeclampsia when mated with human renin-overexpressing males. Females were placed in exercise cages 4 weeks prior to mating, and remained in these throughout gestation. Blood pressure was measured by telemetry, and proteinuria was quantified by ELISA. Placentas were assessed by histology and immunohistochemistry, whereas vascular endothelial growth factor was measured by real-time PCR and immunoblot. Endothelial function was assessed in isolated mesenteric arteries. Conversely to sedentary transgenic females (131.20 ± 4.08 mmHg), trained dam's mean arterial pressure was no longer different from normal mice at the end of gestation (117.5 ± 10.6 vs. 112.3 ± 5.5 mmHg). Proteinuria observed in transgenic dams (3.364 ± 1.62 μg/mg) was absent in trained mice (0.894 ± 0.43 μg/mg). Placental disease and cardiac hypertrophy were also normalized, whereas vascular reactivity was significantly ameliorated. Furthermore, placental vascular endothelial growth factor was normalized in trained transgenic mice. To our knowledge, we are the first to clearly demonstrate that exercise training both before and during gestation can reduce preeclampsia features in a mouse model. Consequently, women at risk for this disease could benefit from exercise training to protect themselves and their future fetuses.

A mobile cage facilitates periodic social contact and exercise for singly caged adult Vervet monkeys.

A mobile exercise cage that expands the quantity and improves the quality of the space available to singly caged adult Vervet monkey males is described. It was easily fitted into an existing caging system and the addition of a resident consort female made it possible for the males to mate and have regular social contact.

Voluntary wheel running reduced the effects of acute ethanol on activity and avoidance in C57BL/6J mice

C57BL/6J mice were given five weeks of voluntary wheel running and then studied for behavioral impairment after an intoxicating dose of ethanol. Forty-four mice, 22 males and 22 females, were assigned to Wheel (free access to a running wheel in the home cage) or No Wheel conditions. At the end of the training period, animals were removed from the exercise cages and tested for noise avoidance after 2.4 g/kg ethanol (EtOH) or physiological saline (Sal). Mice could avoid 87.5-dB noise by entering and remaining in a randomly designated “safe corner.” In unexercised animals, EtOH caused a strong suppression on locomotor activity and avoidance behavior: No Wheel EtOH mice differed significantly from No Wheel Sal mice on both measures. In exercised animals, EtOH failed to cause significant suppression: Wheel EtOH animals did not differ significantly from Wheel Sal animals on either measure. The present results suggest that prior exercise training may be effective in offsetting the effects of acute ethanol intoxication.

Voluntary exercise: Effects on ethanol-induced sleep in the C57BL/6J mouse

After 5 weeks of voluntary wheel running, C57BL/6J mice were significantly resistant to the sleep-inducing effects of ethanol. Sixty-four mice, 32 males and 32 females, were assigned to wheel (free access to a running wheel in the home cage) or no-wheel conditions. At the end of the training period, the animals were removed from the exercise cages and tested for sensitivity to ethanol (3.16 g/kg, 20% w/v), assessed by loss-of-righting reflex (LORR). Exercised animals showed significantly longer latency to LORR (fall time) and shorter duration of LORR (sleep time). Exercise caused a significant decrease in body weight in male, but not female, mice. The present results suggest that exercise training may be effective in reducing ethanol-induced sleep.

Voluntary exercise: Effects on ethanol-induced sleep in the C57BL/6J mouse

After 5 weeks of voluntary wheel running, C57BL/6J mice were significantly resistant to the sleep-inducing effects of ethanol. Sixty-four mice, 32 males and 32 females, were assigned to wheel (free access to a running wheel in the home cage) or no-wheel conditions. At the end of the training period, the animals were removed from the exercise cages and tested for sensitivity to ethanol (3.16 g/kg, 20% w/v), assessed by loss-of-righting reflex (LORR). Exercised animals showed significantly longer latency to LORR (fall time) and shorter duration of LORR (sleep time). Exercise caused a significant decrease in body weight in male, but not female, mice. The present results suggest that exercise training may be effective in reducing ethanol-induced sleep.

Increased cage size does not alter heart rate or behavior in female rhesus monkeys

AbstractNewly proposed federal regulations will mandate that singly caged non‐human primates be kept in cages larger than the current minimum standard, or be given 4 hours in an exercise cage per week. In order to evaluate the effectiveness of increasing cage size in improving well‐being, the behavioral and heart rate responses of 10 female rhesus monkeys (Macaca mulatta) to three different cage sizes were measured. With the exception of vocalizations, no significant differences in behavior were obtained. Grunts increased in the largest cage, following the birth of an infant in a cage within view of the test cages. No differences with respect to cage size were found in heart rate or activity level, although there were significant variations at different times of day. We conclude that modest increases in cage size are less likely to enrich the environment of singly caged laboratory primates than are changes in social opportunities or increases in environmental complexity.

Voluntary exercise during pregnancy and lactation and its effect on lactational performance in mice.

The amount of voluntary exercise during pregnancy and lactation and its effect on the lactational performance in mice were investigated. Female mice were housed in exercise cages with treadwheels during periods of growth, pregnancy and lactation and the amounts of exercise were measured. It was observed that growing female mice exercised voluntarily at a level of approximately 5,000 rotations (diameter of treadwheel; 13.5 cm) per day during the 4-week growth period. After conception, the amount of exercise gradually decreased and in late pregnancy running activity decreased markedly. Throughout the lactational period dams exercised lightly. As indices of lactational performance, the body weights of pups nursed in litters of 8, milk yield and cellular development of abdominal-inguinal mammary glands were examined. There were no significant differences in the final body weights of pups, milk yield per day or development of mammary glands between exercise and non-exercise groups.

Fiber sizes and capillary to fiber ratios in skeletal muscle of exercised rats.

AbstractThirty male rats (Sprague‐Dawley), 25 days of age, were placed in exercise cages for seven days. They were matched into trios on the basis of the last four days total exercise and randomly placed in three groups: sedentary, spontaneous exercise and forced exercise. For the next 35 days, the sedentary group was permitted no exercise other than that allowed by their small individual cages. The spontaneous group remained in activity cages while the forced group in addition to being in activity cages, swam one 30‐minute period each day with weights equal to 20% of the body weight attached to their tails. At the end of the 35‐day activity period, the animals were sacrificed. The hind limbs were injected with India ink, embedded in gelatin and cut on the freezing microtome. The cross‐sectional area of red and white fibers from the gastrocnemius muscles were measured by using the polar planimeter. Ink‐filled capillaries were counted, in conjuction with fiber measurements.With forced and voluntary exercise programs there was a greater increase in crosssectional area of the red than of the white fibers. Under the same conditions, the increase in the number of capillaries per fiber was greater for white than for red fibers.

An exercise cage designed to enable continuous electrical measurements to be made on small animals

An exercise cage designed to enable continuous electrical measurements to be made on small animals

Enzyme levels in rats adapted to 36-hour fasting

In an attempt to increase the amplitude of the normal daily oscillations in nucleic acid metabolism and enzyme synthesis or activation, male rats were adapted to a feeding program in which food was available for 12 hr in each 48-hr period, with lighting automatically regulated to give alternating 12-hr periods of light and darkness. Thus food was available only during alternate 12-hr periods of darkness. Controls were fed on an ad libitum basis. The “36-hr fasting-adapted” animals showed great physical activity on the nights they were not fed, and when kept in exercise cages traveled an average of 15.3 km per 12-hr period of fasting. The fasting-adapted animals weighed much less than the ad libitum controls, and after 30 days weighed an average of 225 g in contrast to 325 g when both groups began the experiment at 150 g body weight. Glycogen, blood sugar, the activities of glucokinase, hexokinase, glucose-6-phosphate dehydrogenase, citrate cleavage enzyme, tryptophan pyrrolase, tyrosine transaminase, serine deaminase, and ornithine transaminase, and labeling of RNA and DNA in vivo were measured. Several of the enzymes showed great increases in the amplitude of cyclic fluctuations in activity. Some enzymes showed evidence of a parallel fluctuation, while others showed individualized timing in peak activity. The 36-hr fasting-adapted animal may be useful in studies on mechanisms of regulating enzyme synthesis or activation and may suggest how human subjects might undertake a program of stress-conditioning.

Effect of Exercise on Growth and Cataract Development of Rats Fed Galactose.

The high blood galactose and galacturia always found in rats on rations containing as much as 25% galactose,1 raises the question as to the efficiency of the utilization of this sugar for muscular work. A brief study of this problem was made possible by the loan of some revolving exercise cages. The rations were those previously reported and were fed ad lib.Littermates on the 25% galactose diet were divided between stationary and exercise cages as were control animals from the respective litters on a similar diet containing glucose in place of galactose. Exercise was entirely voluntary and the number of revolutions per week was recorded. Basal caloric requirement was calculated from body weight according to the formula of Diack2 and caloric intake from food consumed (4.19 cal. per gram).Growth was remarkably constant and similar for all groups, male and female, with and without exercise, and showed no difference due to type of single sugar in the diet. The calculated extra calories consumed above that req...