Influence of genetic background on daily running-wheel activity differs with aging

2005 ◽  
Vol 22 (1) ◽  
pp. 76-85 ◽  
Author(s):  
Michael J. Turner ◽  
Steven R. Kleeberger ◽  
J. Timothy Lightfoot
Keyword(s):  
Physical Activity ◽  
Genetic Background ◽  
Wheel Running ◽  
Inbred Mice ◽  
Inbred Strains ◽  
Broad Sense ◽  
Broad Sense Heritability ◽  
Running Wheel ◽  
Age Related ◽  
Wheel Activity

In humans, physical activity declines with age. We tested the hypothesis that genetic background and age interact to determine daily wheel-running physical activity patterns in mice. Five female mice from ten inbred strains (A/J, AKR/J, Balb/cJ, CBA/J, C3H/HeJ, C3Heb/FeJ, C57Bl/6J, C57L/J, DBA/2J, and SWR/J) were studied for 26 wk starting at 10 wk of age. All mice were housed in separate cages, each with a running wheel and magnetic sensor. Throughout the 26-wk period, age-related change in daily duration ( P < 0.0001), daily distance ( P < 0.0001), and average velocity ( P = 0.0003) differed between the inbred strains. Unlike the other strains, SWR/J mice increased their running-wheel activity throughout the 6-mo time period. Broad-sense heritability estimations for the strains across the 26-wk period ranged between 0.410 and 0.855 for the three physical activity phenotypes. Furthermore, the broad-sense heritability estimates for daily running-wheel distance differed across time and suggested an interaction between genetic background and age on physical activity in these inbred mice.

scholarly journals Exercise opens a temporal window for enhanced cognitive improvement from subsequent physical activity

2019 ◽  
Vol 26 (12) ◽  
pp. 485-492
Author(s):  
Christopher W. Butler ◽  
Ashley A. Keiser ◽  
Janine L. Kwapis ◽  
Nicole C. Berchtold ◽  
Vanessa L. Wall ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cognitive Enhancement ◽  
Wheel Running ◽  
Initial Period ◽  
Object Location ◽  
Running Wheel ◽  
Temporal Window ◽  
Cognitive Improvement ◽  
Exercise Induced

The beneficial effects of exercise on cognition are well established; however specific exercise parameters regarding the frequency and duration of physical activity that provide optimal cognitive health have not been well defined. Here, we explore the effects of the duration of exercise and sedentary periods on long-term object location memory (OLM) in mice. We use a weak object location training paradigm that is subthreshold for long-term memory formation in sedentary controls, and demonstrate that exercise enables long-term memories to form. We show that 14- and 21-d of running wheel access enables mice to discriminate between familiar and novel object locations after a 24 h delay, while 2- or 7-d running wheel access provides insufficient exercise for such memory enhancement using the subthreshold learning paradigm. After 14- and 21-d of wheel running, exercise-induced cognitive enhancement then decays back to baseline performance following 3-d of sedentary activity. However, exercise-induced cognitive enhancement can be reactivated by an additional period of just 2 d exercise, previously shown to be insufficient to induce cognitive enhancement on its own. The reactivating period of exercise is capable of enhancing memory after three- or seven-sedentary days, but not 14-d. These data suggest a type of “molecular memory” for the exercise stimulus, in that once exercise duration reaches a certain threshold, it establishes a temporal window during which subsequent low-level exercise can capitalize on the neurobiological adaptations induced by the initial period of exercise, enabling it to maintain the benefits on cognitive function. These findings provide new information that may help to guide future clinical studies in exercise.

Age Of Running Wheel Exposure Alters Wheel Activity Of Female Inbred Mice

2005 ◽  
Vol 37 (Supplement) ◽  
pp. S439
Author(s):  
Alan P. Jung ◽  
Tamera S. Curtis ◽  
Michael J. Tumer
Keyword(s):  
Inbred Mice ◽  
Running Wheel ◽  
Wheel Activity

Age Of Running Wheel Exposure Alters Wheel Activity Of Female Inbred Mice

2005 ◽  
Vol 37 (Supplement) ◽  
pp. S439
Author(s):  
Alan P. Jung ◽  
Tamera S. Curtis ◽  
Michael J. Tumer
Keyword(s):  
Inbred Mice ◽  
Running Wheel ◽  
Wheel Activity

scholarly journals Substrains of Inbred Mice Differ in Their Physical Activity as a Behavior

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Dario Coletti ◽  
Emanuele Berardi ◽  
Paola Aulino ◽  
Eleonora Rossi ◽  
Viviana Moresi ◽  
...  
Keyword(s):  
Physical Activity ◽  
Wheel Running ◽  
Average Distance ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Inbred Mouse Strain ◽  
Time Frame ◽  
Mouse Strains ◽  
Muscle Adaptation ◽  
Voluntary Activity

Recent studies strengthen the belief that physical activity as a behavior has a genetic basis. Screening wheel-running behavior in inbred mouse strains highlighted differences among strains, showing that even very limited genetic differences deeply affect mouse behavior. We extended this observation to substrains of the same inbred mouse strain, that is, BALB/c mice. We found that only a minority of the population of one of these substrains, the BALB/c J, performs spontaneous physical activity. In addition, the runners of this substrain cover a significantly smaller distance than the average runners of two other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows a striking level of voluntary activity, with the average distance run/day reaching up to about 12 kilometers. These runners are not outstanders, but they represent the majority of the population, with important scientific and economic fallouts to be taken into account during experimental planning. Spontaneous activity persists in pathological conditions, such as cancer-associated cachexia. This important amount of physical activity results in a minor muscle adaptation to endurance exercise over a three-week period; indeed, only a nonsignificant increase in NADH transferase+ fibers occurs in this time frame.

Genetic influence on daily wheel running activity level

2004 ◽  
Vol 19 (3) ◽  
pp. 270-276 ◽  
Author(s):  
J. Timothy Lightfoot ◽  
Michael J. Turner ◽  
Meredith Daves ◽  
Anna Vordermark ◽  
Steven R. Kleeberger
Keyword(s):  
Wheel Running ◽  
Activity Level ◽  
Male Mice ◽  
Running Wheel ◽  
Female Mice ◽  
Running Activity ◽  
Daily Exercise ◽  
Wheel Running Activity ◽  
Wheel Activity ◽  
Daily Distance

This project was designed to determine the genetic (between-strain) and environmental (within-strain) variance in daily running wheel activity level in inbred mice. Five male and five female mice, 9.7–15.3 wk old, from each of 13 strains (A/J, AKR/J, BALB/cJ, C3H/HeJ, C57Bl/6J, C57L/J, C3Heb/FeJ, CBA/J, DBA/2J, SWR/J, MRL/MpJ, SPRET/Ei, and CAST/Ei) as well as five female NZB/BinJ mice were housed individually. A running wheel in each cage was interfaced with a magnetic sensor to measure total daily distance and exercise time for each animal every 24 h for 21 consecutive days (3 wk). Average daily distance (km), duration (min), and velocity (m/min) for each strain was then calculated. Significant interstrain differences in average daily distance ( P < 0.001), average daily exercise duration ( P < 0.0001), and average daily exercise velocity ( P < 0.0001) were found, with C57L/J mice running farther and faster than the other strains. Sex was a significant factor in daily running wheel activity, with female mice running an average of 20% farther ( P = 0.01) and 38% faster ( P < 0.0001) than male mice. The male mice ran 15% longer duration on a daily basis ( P = 0.0091). Weight was only associated with exercise velocity in the female mice, but this relationship was not significant when subdivided by strain. Broad-sense heritability estimates on the physical activity differed by sex (for distance, male 31–48% and female 12–22%; for duration, male 44–61% and female 12–21%; for velocity, male 49–66% and female 44–61%). In conclusion, these data indicate that daily running wheel activity level in mice is significantly affected by genetic background and sex.

scholarly journals Untypical Metabolic Adaptations in Spontaneously Hypertensive Rats to Free Running Wheel Activity Includes Uncoupling Protein-3 (UCP-3) and Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Expression

2021 ◽  
Vol 12 ◽  
Author(s):  
Annemarie Wolf ◽  
Hanna Sarah Kutsche ◽  
Felix Atmanspacher ◽  
Meryem Sevval Karadedeli ◽  
Rolf Schreckenberg ◽  
...  
Keyword(s):  
Physical Activity ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
Glut 1 ◽  
Hepatic Expression ◽  
Glut 4 ◽  
Metabolic Adaptations ◽  
Free Running ◽  
Wheel Activity

Obesity and hypertension are common risk factors for cardiovascular disease whereas an active lifestyle is considered as protective. However, the interaction between high physical activity and hypertension is less clear. Therefore, this study investigates the impact of high physical activity on the muscular and hepatic expression of glucose transporters (Glut), uncoupling proteins (UCPs), and proprotein convertase subtilisin/kexin type 9 (PCSK9) in spontaneously hypertensive rats (SHRs). Twenty-four female rats (12 normotensive rats and 12 SHRs) were divided into a sedentary control and an exercising group that had free access to running wheels at night for 10 months. Blood samples were taken and blood pressure was determined. The amount of visceral fat was semi-quantitatively analyzed and Musculus gastrocnemius, Musculus soleus, and the liver were excised. Acute effects of free running wheel activity were analyzed in 15 female SHRs that were sacrificed after 2 days of free running wheel activity. M. gastrocnemius and M. soleus differed in their mRNA expression of UCP-2, UCP-3, GLUT-4, and PCSK9. Hypertension was associated with lower levels of UCP-2 and PCSK9 mRNA in the M. gastrocnemius, but increased expression of GLUT-1 and GLUT-4 in the M. soleus. Exercise down-regulated UCP-3 in the M. soleus in both strains, in the M. gastrocnemius only in normotensives. In SHRs exercise downregulated the expression of UCP-2 in the M. soleus. Exercise increased the expression of GLUT-1 in the M. gastrocnemius in both strains, and that of GLUT-4 protein in the M. soleus, whereas it increased the muscle-specific expression of PCSK9 only in normotensive rats. Effects of exercise on the hepatic expression of cholesterol transporters were seen only in SHRs. As an acute response to exercise increased expressions of the myokine IL-6 and that of GLUT-1 were found in the muscles. This study, based on transcriptional adaptations in striated muscles and livers, shows that rats perform long-term metabolic adaptations when kept with increased physical activity. These adaptations are at least in part required to stabilize normal protein expression as protein turnover seems to be modified by exercise. However, normotensive and hypertensive rats differed in their responsiveness. Based on these results, a direct translation from normotensive to hypertensive rats is not possible. As genetic differences between normotensive humans and patients with essential hypertension are likely to be present as well, we would expect similar differences in humans that may impact recommendations for non-pharmacological interventions.

scholarly journals Pro-inflammatory Vascular Stress in Spontaneously Hypertensive Rats Associated With High Physical Activity Cannot Be Attenuated by Aldosterone Blockade

2021 ◽  
Vol 8 ◽  
Author(s):  
Rolf Schreckenberg ◽  
Annemarie Wolf ◽  
Christian Troidl ◽  
Sakine Simsekyilmaz ◽  
Klaus-Dieter Schlüter
Keyword(s):  
Physical Activity ◽  
Vascular Wall ◽  
Hypertensive Rats ◽  
Running Wheel ◽  
Spontaneously Hypertensive ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Voluntary Running ◽  
Running Wheel Exercise ◽  
Wheel Activity

The effect of high physical activity, performed as voluntary running wheel exercise, on inflammation and vascular adaptation may differ between normotensive and spontaneously hypertensive rats (SHRs). We investigated the effects of running wheel activity on leukocyte mobilization, neutrophil migration into the vascular wall (aorta), and transcriptional adaptation of the vascular wall and compared and combined the effects of high physical activity with that of pharmacological treatment (aldosterone antagonist spironolactone). At the start of the 6th week of life, before hypertension became established in SHRs, rats were provided with a running wheel over a period of 10-months'. To investigate to what extent training-induced changes may underlie a possible regression, controls were also generated by removal of the running wheel for the last 4 months. Aldosterone blockade was achieved upon oral administration of Spironolactone in the corresponding treatment groups for the last 4 months. The number of circulating blood cells was quantified by FACS analysis of peripheral blood. mRNA expression of selected proteins was quantified by RT-PCR. Histology and confocal laser microscopy were used to monitor cell migration. Although voluntary running wheel exercise reduced the number of circulating neutrophils in normotensive rats, it rather increased it in SHRs. Furthermore, running wheel activity in SHRs but not normotensive rats increased the number of natural killer (NK)-cells. Except of the increased expression of plasminogen activator inhibitor (PAI)-1 and reduction of von Willebrand factor (vWF), running wheel activity exerted a different transcriptional response in the vascular tissue of normotensive and hypertensive rats, i.e., lack of reduction of the pro-inflammatory IL-6 in vessels from hypertensive rats. Spironolactone reduced the number of neutrophils; however, in co-presence with high physical activity this effect was blunted. In conclusion, although high physical activity has beneficial effects in normotensive rats, this does not predict similar beneficial effects in the concomitant presence of hypertension and care has to be taken on interactions between pharmacological approaches and high physical activity in hypertensives.

P6372Does modification of activity regimes optimize the effect of high physical activity on hypertensive heart disease?

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K.-D Schluter ◽  
R Schreckenberg ◽  
A Wolf ◽  
H Kutsche ◽  
C Troidl ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Life Style ◽  
Work Load ◽  
Running Wheel ◽  
High Physical Activity ◽  
Beneficial Effects ◽  
Active Life ◽  
Free Running ◽  
Wheel Activity

Abstract Aims and background Spontaneously hypertensive rats (SHR) are a suitable model of essential hypertension and allow analyze the progression of hypertension and hypertension-dependent end-organ damage. In this model, acute improvement of physical activity (free running wheel activity) exerts known beneficial effects (such as lowering oxidative stress). However, these initial beneficial effects are lost during the continuation of high physical activity and translate into mal-adaptive processes, suggesting that not any high physical activity exerts beneficial effects. It has been hypothesized that the skeletal muscle release myokines, that contribute to the beneficial effects of exercise. However, myokines, such as IL-6, are induced by an acute increase in work load not by continuous work load. Therefore, we analyzed whether modification of high physical activity, i.e. intermittent free running wheel activity, modify the long-term impact on long lasting hypertension. Methods 38 female SHR aged 6 weeks (pre-hypertensive state) were randomly allocated to one of the following groups: Sedentary (S; standard holding condition) imitating the condition of sedentary life style, high activity (HA; life-long free running wheel) imitating the condition of active life style, temporary activity (TA; 6 months free running wheel and 3 months sedentary) imitating the loss of active life style during ageing, and finally intermittent activity (IA; 10 months repetitive access to running wheels every 4 weeks) imitating altered workloads. All rats were sacrificed at the age of 10 months. Results IA was the only treatment regime that effectively lowered blood pressure (P syst: 186±11 vs. 165±6 mmHg), improved ejection fraction (EF: 56±5 vs. 63±2%), and displayed clear molecular profile of adaptive myocardial hypertrophy rather than mal-adaptive hypertrophy. Moreover, only IA reduced the number of circulating monocytes (377±102 vs. 220±16 /μl), a cell population that immigrated in the left ventricle. The number of monocytes was directly correlated with the expression of MMP12, BNP, ANP, biglycan, collagen-1, actinin, β-MHC, and somatstatin but inversely related to β-adrenoceptor, Glut-4, and UCP3 expression. Finally, IA increased the skeletal expression of IL-6 and decreased the renal expression of AT1 receptors. Conclusion The data confirm the previous findings that not all type of physical activity beneficially affects hypertensive-dependent disease. In contrast, the data support the hypothesis that alterations in work load are required triggering the release of myokines from the skeletal muscle and identify the amount of circulating monocytes as a main trigger of mal-adaptive hypertrophy in these rats. The data are important with respect to optimize life style suggestions for patients with essential hypertension. Acknowledgement/Funding DFG (ERAGON and SFB 1213)

Genetic variability in the development of pulmonary tolerance to inhaled pollutants in inbred mice

2001 ◽  
Vol 281 (5) ◽  
pp. L1200-L1209 ◽  
Author(s):  
Scott C. Wesselkamper ◽  
Lung Chi Chen ◽  
Steven R. Kleeberger ◽  
Terry Gordon
Keyword(s):  
Polymorphonuclear Leukocyte ◽  
Genetic Background ◽  
Bronchoalveolar Lavage Fluid ◽  
Inbred Mice ◽  
Inbred Strains ◽  
Lavage Fluid ◽  
Toxic Compound ◽  
Adverse Health Effects ◽  
Protein Levels ◽  
Inbred Strains Of Mice

After repeated exposures, many individuals develop tolerance to the adverse health effects of inhaled pollutants. Pulmonary tolerance can be characterized as the ability of the lung to withstand the adverse actions of a toxic compound after repeated exposures. To determine whether genetic background is important to the development of pulmonary tolerance to inhaled pollutants, 11 inbred strains of mice were exposed once (1×) or for 5 consecutive days (5×) to 1.0 mg/m3of zinc oxide (ZnO). Development of pulmonary tolerance was assessed by measuring polymorphonuclear leukocyte and protein levels in bronchoalveolar lavage fluid and comparing the responses of the 1× and 5× groups. Significant interstrain variation in polymorphonuclear leukocyte and protein responses was observed between the groups with 1× and 5× exposures, which indicates that genetic background has an important role in the development of pulmonary tolerance. The BALB/cByJ strain and the DBA/2J strain were the most tolerant and nontolerant, respectively. The CByD2F1/J offspring were uniformly nontolerant. The development of tolerance was also investigated in BALB/cByJ and DBA/2J mice after 1× and 5× exposure to ozone and aerosolized endotoxin. Discordance in the phenotypic pattern of pulmonary tolerance among strains after exposure to ZnO, ozone, and endotoxin suggested that different mechanisms may be responsible for the development of pulmonary tolerance to these agents.

scholarly journals High-throughput sleep phenotyping produces robust and heritable traits in Diversity Outbred mice and their founder strains

SLEEP ◽  
2020 ◽  
Vol 43 (5) ◽  
Author(s):  
Brendan T Keenan ◽  
Raymond J Galante ◽  
Jie Lian ◽  
Petr Simecek ◽  
Daniel M Gatti ◽  
...  
Keyword(s):  
High Throughput ◽  
Genetic Factors ◽  
Wheel Running ◽  
Sleep Latency ◽  
Phenotypic Variability ◽  
Genetic Effects ◽  
Broad Sense ◽  
Broad Sense Heritability ◽  
Diversity Outbred ◽  
High Throughput Phenotyping

Abstract Study Objectives This study describes high-throughput phenotyping strategies for sleep and circadian behavior in mice, including examinations of robustness, reliability, and heritability among Diversity Outbred (DO) mice and their eight founder strains. Methods We performed high-throughput sleep and circadian phenotyping in male mice from the DO population (n = 338) and their eight founder strains: A/J (n = 6), C57BL/6J (n = 14), 129S1/SvlmJ (n = 6), NOD/LtJ (n = 6), NZO/H1LtJ (n = 6), CAST/EiJ (n = 8), PWK/PhJ (n = 8), and WSB/EiJ (n = 6). Using infrared beam break systems, we defined sleep as at least 40 s of continuous inactivity and quantified sleep–wake amounts and bout characteristics. We developed assays to measure sleep latency in a new environment and during a modified Murine Multiple Sleep Latency Test, and estimated circadian period from wheel-running experiments. For each trait, broad-sense heritability (proportion of variability explained by all genetic factors) was derived in founder strains, while narrow-sense heritability (proportion of variability explained by additive genetic effects) was calculated in DO mice. Results Phenotypes were robust to different inactivity durations to define sleep. Differences across founder strains and moderate/high broad-sense heritability were observed for most traits. There was large phenotypic variability among DO mice, and phenotypes were reliable, although estimates of heritability were lower than in founder mice. This likely reflects important nonadditive genetic effects. Conclusions A high-throughput phenotyping strategy in mice, based primarily on monitoring of activity patterns, provides reliable and heritable estimates of sleep and circadian traits. This approach is suitable for discovery analyses in DO mice, where genetic factors explain some proportion of phenotypic variation.

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