scholarly journals Antioxidant Gene Expression in Active and Sedentary House Mice (Mus domesticus) Selected for High Voluntary Wheel-Running Behavior

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1763-1769 ◽  
Author(s):  
Anne M Bronikowski ◽  
Theodore J Morgan ◽  
Theodore Garland ◽  
Patrick A Carter

Abstract We present liver mRNA levels of the two antioxidant enzymes catalase (CAT) and Mn-superoxide dismutase (SOD2) in four treatment groups of house mice assayed by RNase protection at 20 months of age. These groups were mice from four replicate selection and four replicate control lines from the sixteenth generation of selective breeding for high voluntary wheel running, housed with or without running wheels from age 3 weeks through 20 months. Exercising control females had induced CAT expression; SOD2 exhibited a similar pattern in females from two of the four control lines. Exercising male mice had induced CAT expression, but not SOD2 expression, irrespective of genetic background. We discuss these results with respect to both evolutionary (genetic) and training (exercise-induced) adaptations and explore predictions of these results in relation to the oxidative-damage theory of senescence.

2020 ◽  
Author(s):  
Rachel P. Tillage ◽  
Genevieve E. Wilson ◽  
L. Cameron Liles ◽  
Philip V. Holmes ◽  
David Weinshenker

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.


2000 ◽  
Vol 89 (4) ◽  
pp. 1608-1616 ◽  
Author(s):  
Philippe Houle-Leroy ◽  
Theodore Garland ◽  
John G. Swallow ◽  
Helga Guderley

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.


2001 ◽  
Vol 204 (24) ◽  
pp. 4311-4320 ◽  
Author(s):  
I. Girard ◽  
M. W. McAleer ◽  
J. S. Rhodes ◽  
T. Garland

SUMMARY In nature, many animals use intermittent rather than continuous locomotion. In laboratory studies, intermittent exercise regimens have been shown to increase endurance compared with continuous exercise. We hypothesized that increased intermittency has evolved in lines of house mice (Mus domesticus) that have been selectively bred for high voluntary wheel-running (wheel diameter 1.12 m) activity. After 23 generations, female mice from four replicate selection lines ran 2.7 times more revolutions per day than individuals from four random-bred control lines. To measure instantaneous running speeds and to quantify intermittency, we videotaped mice (N=41) during a 5-min period of peak activity on night 6 of a 6-day exposure to wheels. Compared with controls (20 revs min–1 while actually running), selection-line females (41 revs min–1) ran significantly faster. These instantaneous speeds closely matched the computer-recorded speeds over the same 5-min period. Selection-line females also ran more intermittently, with shorter (10.0 s bout–1) and more frequent (7.8 bouts min–1) bouts than controls (16.8 s bout–1, 3.4 bouts min–1). Inter-bout pauses were also significantly shorter in selection-line (2.7 s) than in control-line (7.4 s) females. We hypothesize that intermittency of locomotion is a key feature allowing the increased wheel-running performance at high running speeds in selection-line mice.


2018 ◽  
Vol 233 (2) ◽  
pp. 193-203 ◽  
Author(s):  
Nicolas L. Schwartz ◽  
Biren A. Patel ◽  
Theodore Garland ◽  
Angela M. Horner

2013 ◽  
Vol 216 (22) ◽  
pp. 4212-4221 ◽  
Author(s):  
E. M. Dlugosz ◽  
H. Schutz ◽  
T. H. Meek ◽  
W. Acosta ◽  
C. J. Downs ◽  
...  

1999 ◽  
Vol 58 (6) ◽  
pp. 1307-1318 ◽  
Author(s):  
Paweł Koteja ◽  
Theodore Garland ◽  
Joanna K. Sax ◽  
John G. Swallow ◽  
Patrick A. Carter

1999 ◽  
Vol 202 (18) ◽  
pp. 2513-2520 ◽  
Author(s):  
J.G. Swallow ◽  
P. Koteja ◽  
P.A. Carter ◽  
T. Garland

To test the hypothesis that body size and activity levels are negatively genetically correlated, we conducted an artificial selection experiment for increased voluntary wheel-running activity in house mice (Mus domesticus). Here, we compare body masses of mice from control and selected lines after 14 generations of selection. In both groups, beginning at weaning and then for 8 weeks, we housed half of the individuals with access to running wheels that were free to rotate and the other half with wheels that were locked to prevent rotation. Mice from selected lines were more active than controls at weaning (21 days) and across the experiment (total revolutions during last week: females 2.5-fold higher, males 2.1-fold higher). At weaning, mice from selected and control lines did not differ significantly in body mass. At 79 days of age, mice from selected lines weighed 13.6 % less than mice from control lines, whereas mice with access to free wheels weighed 4.5 % less than ‘sedentary’ individuals; both effects were statistically significant and additive. Within the free-wheel-access group, individual variation in body mass of males was negatively correlated with amount of wheel-running during the last week (P&lt;0.01); for females, the relationship was also negative but not statistically significant (P&gt;0.40). The narrow-sense genetic correlation between wheel-running and body mass after 8 weeks of wheel access was estimated to be −0. 50. A negative genetic correlation could account for the negative relationship between voluntary wheel-running and body mass that has been reported across 13 species of muroid rodents.


PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261662
Author(s):  
Nora Weegh ◽  
Eva Zentrich ◽  
Dietmar Zechner ◽  
Birgitta Struve ◽  
Laura Wassermann ◽  
...  

Laboratory animals frequently undergo routine experimental procedures such as handling, restraining and injections. However, as a known source of stress, these procedures potentially impact study outcome and data quality. In the present study, we, therefore, performed an evidence-based severity assessment of experimental procedures used in a pancreatic cancer model including surgical tumour induction and subsequent chemotherapeutic treatment via repeated intraperitoneal injections. Cancer cell injection into the pancreas was performed during a laparotomy under general anaesthesia. After a four-day recovery phase, mice received either drug treatment (galloflavin and metformin) or the respective vehicle substances via daily intraperitoneal injections. In addition to clinical scoring, an automated home-cage monitoring system was used to assess voluntary wheel running (VWR) behaviour as an indicator of impaired well-being. After surgery, slightly elevated clinical scores and minimal body weight reductions, but significantly decreased VWR behaviour were observed. During therapy, body weight declined in response to chemotherapy, but not after vehicle substance injection, while VWR activity was decreased in both cases. VWR behaviour differed between treatment groups and revealed altered nightly activity patterns. In summary, by monitoring VWR a high impact of repeated injections on the well-being of mice was revealed and substance effects on well-being were distinguishable. However, no differences in tumour growth between treatment groups were observed. This might be due to the severity of the procedures uncovered in this study, as exaggerated stress responses are potentially confounding factors in preclinical studies. Finally, VWR was a more sensitive indicator of impairment than clinical scoring in this model.


2018 ◽  
Author(s):  
Peter van Lunteren ◽  
Marnix A. Groenewold ◽  
Gabor Pozsgai ◽  
Joseph Sarvary

AbstractRunning wheels are frequently used to improve the welfare of captive animals, increase environmental enrichment, and, by doing so, reduce stereotypic behaviors. It is, however, still debated whether or not wheel running itself is a stereotypy. New evidence emerged when Meijer and Robbers (2014, Proc. Royal Soc. B) reported voluntary wheel running of wild animals in the Netherlands. Since stereotypic behaviors are exclusively attributed to captive animals, the occurrence of wheel running in the wild suggests that this behavior is non-stereotypic. Our study explores that same line of investigation, examining whether wild animals will voluntarily use running wheels in a natural area in Paraguay in comparison to the urban and semi-urban settings in the Netherlands. Of the 1857 small mammal visits we recorded, only two occasions showed evidence of what could be considered as wheel running behavior; over hundredfold fewer than previously reported. The potential reasons for the observed difference in wheel running activity, such as different species pool or seasonality, are discussed. The difference, however, is likely to be due to the much lower probability of Neotropical mammals in a remote natural site encountering man-made objects and experiencing urbanization-related behavioral patterns. Additionally, in the light of our findings, we review the definition of wheel running as a stereotypic behavior.


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