The medial prefrontal cortex and nucleus accumbens mediate the motivation for voluntary wheel running in the rat.

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Basso, Julia C; Morrell, Joan I

2015-08-01

Voluntary wheel running in rats provides a preclinical model of exercise motivation in humans. We hypothesized that rats run because this activity has positive incentive salience in both the acquisition and habitual stages of wheel running and that gender differences might be present. Additionally, we sought to determine which forebrain regions are essential for the motivational processes underlying wheel running in rats. The motivation for voluntary wheel running in male and female Sprague-Dawley rats was investigated during the acquisition (Days 1-7) and habitual phases (after Day 21) of running using conditioned place preference (CPP) and the reinstatement (rebound) response after forced abstinence, respectively. Both genders displayed a strong CPP for the acquisition phase and a strong rebound response to wheel deprivation during the habitual phase, suggesting that both phases of wheel running are rewarding for both sexes. Female rats showed a 1.5 times greater rebound response than males to wheel deprivation in the habitual phase of running, while during the acquisition phase, no gender differences in CPP were found. We transiently inactivated the medial prefrontal cortex (mPFC) or the nucleus accumbens (NA), hypothesizing that because these regions are involved in the acquisition and reinstatement of self-administration of both natural and pharmacological stimuli, they might also serve a role in the motivation to wheel run. Inactivation of either structure decreased the rebound response in the habitual phase of running, demonstrating that these structures are involved in the motivation for this behavior. (c) 2015 APA, all rights reserved).

Locomotor trade-offs in mice selectively bred for high voluntary wheel running.

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Dlugosz, Elizabeth M; Chappell, Mark A; McGillivray, David G; Syme, Douglas A; Garland, Theodore

2009-08-01

We investigated sprint performance and running economy of a unique ;mini-muscle' phenotype that evolved in response to selection for high voluntary wheel running in laboratory mice (Mus domesticus). Mice from four replicate selected (S) lines run nearly three times as far per day as four control lines. The mini-muscle phenotype, resulting from an initially rare autosomal recessive allele, has been favoured by the selection protocol, becoming fixed in one of the two S lines in which it occurred. In homozygotes, hindlimb muscle mass is halved, mass-specific muscle oxidative capacity is doubled, and the medial gastrocnemius exhibits about half the mass-specific isotonic power, less than half the mass-specific cyclic work and power, but doubled fatigue resistance. We hypothesized that mini-muscle mice would have a lower whole-animal energy cost of transport (COT), resulting from lower costs of cycling their lighter limbs, and reduced sprint speed, from reduced maximal force production. We measured sprint speed on a racetrack and slopes (incremental COT, or iCOT) and intercepts of the metabolic rate versus speed relationship during voluntary wheel running in 10 mini-muscle and 20 normal S-line females. Mini-muscle mice ran faster and farther on wheels, but for less time per day. Mini-muscle mice had significantly lower sprint speeds, indicating a functional trade-off. However, contrary to predictions, mini-muscle mice had higher COT, mainly because of higher zero-speed intercepts and postural costs (intercept-resting metabolic rate). Thus, mice with altered limb morphology after intense selection for running long distances do not necessarily run more economically.

Reduced metabolic disease risk profile by voluntary wheel running accompanying juvenile Western diet in rats bred for high and low voluntary exercise.

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Ruegsegger, Gregory N; Toedebusch, Ryan G; Braselton, Joshua F; Roberts, Christian K; Booth, Frank W

2015-12-01

Metabolic disease risk is influenced by genetics and modifiable factors, such as physical activity and diet. Beginning at 6 weeks of age, rats selectively bred for high (HVR) versus low voluntary running distance (LVR) behaviors were housed in a complex design with or without voluntary running wheels being fed either a standard or Western (WD, 42% kcal from fat and added sucrose) diet for 8 weeks. Upon intervention completion, percent body fat, leptin, insulin, and mediobasal hypothalamic mRNAs related to appetite control were assessed. Wheel access led to differences in body weight, food intake, and serum leptin and insulin. Intriguingly, percent body fat, leptin, and insulin did not differ between HVR and LVR lines in response to the two levels of voluntary running, regardless of diet, after the 8 wk. experiment despite HVR eating more calories than LVR regardless of diet and voluntarily running 5-7 times further in wheels than LVR. In response to WD, we observed increases in Cart and Lepr mediobasal hypothalamic mRNA in HVR, but no differences in LVR. Npy mRNA was intrinsically greater in LVR than HVR, while wheel access led to greater Pomc and Cart mRNA in LVR versus HVR. These data suggest that despite greater consumption of WD, HVR animals respond similarly to WD as LVR as a result, in part, of their increased wheel running behavior. Furthermore, high physical activity in HVR may offset the deleterious effects of a WD on adiposity despite greater energy intake in this group. Copyright © 2015 Elsevier Inc. All rights reserved.

Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice.

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Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J F; Kuipers, Folkert; Groen, Albert K

2011-10-01

Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in hypercholesterolemic mice. Male LDLR-deficient mice (8 weeks old) had either access to a voluntary running wheel for 12 weeks (RUN) or remained sedentary (CONTROL). Both groups were fed a western-type/high cholesterol diet. Running activity and food intake were recorded. At 12 weeks of intervention, feces, bile and plasma were collected to determine fecal, biliary and plasma parameters of cholesterol metabolism and plasma cytokines. Atherosclerotic lesion size was determined in the aortic root. RUN weighed less (∼13%) while food consumption was increased by 17% (p=0.004). Plasma cholesterol levels were decreased by 12% (p=0.035) and plasma levels of pro-atherogenic lipoproteins decreased in RUN compared to control. Running modulated cholesterol catabolism by enhancing cholesterol turnover: RUN displayed an increased biliary bile acid secretion (68%, p=0.007) and increased fecal bile acid (93%, p=0.009) and neutral sterol (33%, p=0.002) outputs compared to control indicating that reverse cholesterol transport was increased in RUN. Importantly, aortic lesion size was decreased by ∼33% in RUN (p=0.033). Voluntary wheel running reduces atherosclerotic burden in hypercholesterolemic mice. An increased cholesterol turnover, specifically its conversion into bile acids, may underlie the beneficial effect of voluntary exercise in mice. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Are voluntary wheel running and open-field behavior correlated in mice? Different answers from comparative and artificial selection approaches.

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Careau, Vincent; Bininda-Emonds, Olaf R P; Ordonez, Genesis; Garland, Theodore

2012-09-01

Voluntary wheel running and open-field behavior are probably the two most widely used measures of locomotion in laboratory rodents. We tested whether these two behaviors are correlated in mice using two approaches: the phylogenetic comparative method using inbred strains of mice and an ongoing artificial selection experiment on voluntary wheel running. After taking into account the measurement error and phylogenetic relationships among inbred strains, we obtained a significant positive correlation between distance run on wheels and distance moved in the open-field for both sexes. Thigmotaxis was negatively correlated with distance run on wheels in females but not in males. By contrast, mice from four replicate lines bred for high wheel running did not differ in either distance covered or thigmotaxis in the open field as compared with mice from four non-selected control lines. Overall, results obtained in the selection experiment were generally opposite to those observed among inbred strains. Possible reasons for this discrepancy are discussed.

Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression.

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Park, Young-Min; Kanaley, Jill A; Padilla, Jaume; Zidon, Terese; Welly, Rebecca J; Will, Matthew J; Britton, Steven L; Koch, Lauren G; Ruegsegger, Gregory N; Booth, Frank W; Thyfault, John P; Vieira-Potter, Victoria J

2016-10-01

Rats selectively bred for high (HCR) and low (LCR) aerobic capacity show a stark divergence in wheel running behavior, which may be associated with the dopamine (DA) system in the brain. HCR possess greater motivation for voluntary running along with greater brain DA activity compared to LCR. We recently demonstrated that HCR are not immune to ovariectomy (OVX)-associated reductions in spontaneous cage (i.e. locomotor) activity. Whether HCR and LCR rats differ in their OVX-mediated voluntary wheel running response is unknown. To determine whether HCR are protected from OVX-associated reduction in voluntary wheel running. Forty female HCR and LCR rats (age ~27weeks) had either SHM or OVX operations, and given access to a running wheel for 11weeks. Weekly wheel running distance was monitored throughout the intervention. Nucleus accumbens (NAc) was assessed for mRNA expression of DA receptors at sacrifice. Compared to LCR, HCR ran greater distance and had greater ratio of excitatory/inhibitory DA mRNA expression (both line main effects, PWheel running distance was significantly, positively correlated with the ratio of excitatory/inhibitory DA mRNA expression across animals. In both lines, OVX reduced wheel running (Pwheel running, they had greater OVX-induced reduction in wheel running than LCR such that no differences were found 11weeks after OVX between HCROVX and LCROVX (interaction, Pwheel running in HCR was associated with an OVX-mediated reduction in the ratio of excitatory/inhibitory DA mRNA expression. The DA system in the NAc region may play a significant role in motivation to run in female rats. Compared to LCR, HCR rats run significantly more, which associates with greater ratio of excitatory/inhibitory DA mRNA expression. However, despite greater inherent motivation to run and an associated brain DA mRNA expression profile, HCR rats are not protected against OVX-induced reduction in wheel running or OVX-mediated reduction in the ratio of excitatory

Mu-opioid receptor inhibition decreases voluntary wheel running in a dopamine-dependent manner in rats bred for high voluntary running.

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Ruegsegger, Gregory N; Brown, Jacob D; Kovarik, M Cathleen; Miller, Dennis K; Booth, Frank W

2016-12-17

The mesolimbic dopamine and opioid systems are postulated to influence the central control of physical activity motivation. We utilized selectively bred rats for high (HVR) or low (LVR) voluntary running behavior to examine (1) inherent differences in mu-opioid receptor (Oprm1) expression and function in the nucleus accumbens (NAc), (2) if dopamine-related mRNAs, wheel-running, and food intake are differently influenced by intraperitoneal (i.p.) naltrexone injection in HVR and LVR rats, and (3) if dopamine is required for naltrexone-induced changes in running and feeding behavior in HVR rats. Oprm1 mRNA and protein expression were greater in the NAc of HVR rats, and application of the Oprm1 agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) to dissociated NAc neurons produced greater depolarizing responses in neurons from HVR versus LVR rats. Naltrexone injection dose-dependently decreased wheel running and food intake in HVR, but not LVR, rats. Naltrexone (20mg/kg) decreased tyrosine hydroxylase mRNA in the ventral tegmental area and Fos and Drd5 mRNA in NAc shell of HVR, but not LVR, rats. Additionally, lesion of dopaminergic neurons in the NAc with 6-hydroxydopamine (6-OHDA) ablated the decrease in running, but not food intake, in HVR rats following i.p. naltrexone administration. Collectively, these data suggest the higher levels of running observed in HVR rats, compared to LVR rats, are mediated, in part, by increased mesolimbic opioidergic signaling that requires downstream dopaminergic activity to influence voluntary running, but not food intake. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Mitochondrial haplotypes are not associated with mice selectively bred for high voluntary wheel running.

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Wone, Bernard W M; Yim, Won C; Schutz, Heidi; Meek, Thomas H; Garland, Theodore

2018-04-04

Mitochondrial haplotypes have been associated with human and rodent phenotypes, including nonshivering thermogenesis capacity, learning capability, and disease risk. Although the mammalian mitochondrial D-loop is highly polymorphic, D-loops in laboratory mice are identical, and variation occurs elsewhere mainly between nucleotides 9820 and 9830. Part of this region codes for the tRNA Arg gene and is associated with mitochondrial densities and number of mtDNA copies. We hypothesized that the capacity for high levels of voluntary wheel-running behavior would be associated with mitochondrial haplotype. Here, we analyzed the mtDNA polymorphic region in mice from each of four replicate lines selectively bred for 54 generations for high voluntary wheel running (HR) and from four control lines (Control) randomly bred for 54 generations. Sequencing the polymorphic region revealed a variable number of adenine repeats. Single nucleotide polymorphisms (SNPs) varied from 2 to 3 adenine insertions, resulting in three haplotypes. We found significant genetic differentiations between the HR and Control groups (F st  = 0.779, p ≤ 0.0001), as well as among the replicate lines of mice within groups (F sc  = 0.757, p ≤ 0.0001). Haplotypes, however, were not strongly associated with voluntary wheel running (revolutions run per day), nor with either body mass or litter size. This system provides a useful experimental model to dissect the physiological processes linking mitochondrial, genomic SNPs, epigenetics, or nuclear-mitochondrial cross-talk to exercise activity. Copyright © 2018. Published by Elsevier B.V.

Endurance capacity of mice selectively bred for high voluntary wheel running.

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Meek, Thomas H; Lonquich, Brian P; Hannon, Robert M; Garland, Theodore

2009-09-15

Mice from four lines bred for high voluntary wheel activity run approximately 3-fold more revolutions per day and have elevated maximal oxygen consumption during forced treadmill exercise, as compared with four unselected control (C) lines. We hypothesized that these high runner (HR) lines would have greater treadmill endurance-running capacity. Ninety-six mice from generation 49 were familiarized with running on a motorized treadmill for 3 days. On days 4 and 5, mice were given an incremental speed test (starting at 20 m min(-1), increased 1.5 m min(-1) every 2 min) and endurance was measured as the total time or distance run to exhaustion. Blood samples were taken to measure glucose and lactate concentrations at rest during the photophase, during peak nightly wheel running, and immediately following the second endurance test. Individual differences in endurance time were highly repeatable between days (r=0.79), and mice tended to run longer on the second day (paired t-test, Pwheel running and treadmill endurance differed between the sexes, reinforcing previous studies that indicate sex-specific responses to selective breeding. HR mice appear to have a higher endurance capacity than reported in the literature for inbred strains of mice or transgenics intended to enhance endurance.

Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats

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Schultz, R L; Kullman, E L; Waters, Ryan

2013-01-01

SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function...... robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal...

Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes.

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Thompson, Zoe; Argueta, Donovan; Garland, Theodore; DiPatrizio, Nicholas

2017-03-01

The endocannabinoid system serves many physiological roles, including in the regulation of energy balance, food reward, and voluntary locomotion. Signaling at the cannabinoid type 1 receptor has been specifically implicated in motivation for rodent voluntary exercise on wheels. We studied four replicate lines of high runner (HR) mice that have been selectively bred for 81 generations based on average number of wheel revolutions on days five and six of a six-day period of wheel access. Four additional replicate lines are bred without regard to wheel running, and serve as controls (C) for random genetic effects that may cause divergence among lines. On average, mice from HR lines voluntarily run on wheels three times more than C mice on a daily basis. We tested the general hypothesis that circulating levels of endocannabinoids (i.e., 2-arachidonoylglycerol [2-AG] and anandamide [AEA]) differ between HR and C mice in a sex-specific manner. Fifty male and 50 female mice were allowed access to wheels for six days, while another 50 males and 50 females were kept without access to wheels (half HR, half C for all groups). Blood was collected by cardiac puncture during the time of peak running on the sixth night of wheel access or no wheel access, and later analyzed for 2-AG and AEA content by ultra-performance liquid chromatography coupled to tandem mass spectrometry. We observed a significant three-way interaction among sex, linetype, and wheel access for 2-AG concentrations, with females generally having lower levels than males and wheel access lowering 2-AG levels in some but not all subgroups. The number of wheel revolutions in the minutes or hours immediately prior to sampling did not quantitatively predict plasma 2-AG levels within groups. We also observed a trend for a linetype-by-wheel access interaction for AEA levels, with wheel access lowering plasma concentrations of AEA in HR mice, while raising them in C mice. In addition, females tended to have higher AEA

Voluntary wheel running increases satellite cell abundance and improves recovery from disuse in gastrocnemius muscles from mice.

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Brooks, Matthew J; Hajira, Ameena; Mohamed, Junaith S; Alway, Stephen E

2018-02-22

Reloading of atrophied muscles after hindlimb suspension unloading (HSU) can induce injury and prolong recovery. Low-impact exercise, such as voluntary wheel running, has been identified as a non-damaging rehabilitation therapy in rodents, but its effects on muscle function, morphology, and satellite cell activity after HSU are unclear. This study tested the hypothesis that low impact wheel running would increase satellite cell proliferation and improve recovery of muscle structure and function after HSU in mice. Young adult male and female C57BL/6 mice (n=6/group) were randomly placed into 5 groups. These included HSU without recovery (HSU), normal ambulatory recovery for 14 days after HSU (HSU+NoWR), and voluntary wheel running recovery for 14 days after HSU (HSU+WR). Two control groups were used: non-suspended mice-cage controls (Control) and voluntary wheel running controls (ControlWR). Satellite cell activation, was evaluated by providing mice 5-bromo-2'-deoxyuridine (BrdU) in their drinking water. As expected, HSU significantly reduced in vivo maximal force and decreased the in vivo fatigability and decreased type I and IIa myosin heavy chain (MHC) abundance in plantarflexor muscles. HSU+WR mice significantly improved plantarflexor fatigue resistance, increased type type I and IIa MHC abundance, increased fiber cross sectional area (CSA), and an increased the percentage of type I and IIA muscle fibers in the gastrocnemius muscle. HSU+WR mice also had a significantly greater percentage of BrdU-positive and Pax 7 positive nuclei inside muscle fibers and a greater MyoD to Pax 7 protein ratio when compared to HSU+NoWR mice. The mechanotransduction protein Yes-associated protein (YAP) was elevated with reloading after HSU, but HSU+WR had lower levels of the inactive phosphorylated YAP serine127 which may have contributed to increased satellite cell activation creased with reloading after HSU. These results indicate that voluntary wheel running increased YAP

Wheel running, voluntary ethanol consumption, and hedonic substitution.

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Ozburn, Angela Renee; Harris, R Adron; Blednov, Yuri A

2008-08-01

Few studies have examined the relationship between naturally rewarding behaviors and ethanol drinking behaviors in mice. Although natural and drug reinforcers activate similar brain circuitry, there is behavioral evidence suggesting food and drug rewards differ in perceived value. The primary goal of the present study was to investigate the relationships between naturally reinforcing stimuli and consumption of ethanol in ethanol preferring C57BL/6J mice. Mouse behaviors were observed after the following environmental manipulations: standard or enhanced environment, accessible or inaccessible wheel, and presence or absence of ethanol. Using a high-resolution volumetric drinking monitor and wheel running monitor, we evaluated whether alternating access to wheel running modified ethanol-related behaviors and whether alternating access to ethanol modified wheel running or subsequent ethanol-related behaviors. We found that ethanol consumption remains stable with alternating periods of wheel running. Wheel running increases in the absence of ethanol and decreases upon reintroduction of ethanol. Upon reintroduction of ethanol, an alcohol deprivation effect was seen. Collectively, the results support theories of hedonic substitution and suggest that female C57BL/6J mice express ethanol seeking and craving under these specific conditions.

Loss of Cdk5 function in the nucleus accumbens decreases wheel running and may mediate age‐related declines in voluntary physical activity

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Ruegsegger, Gregory N.; Toedebusch, Ryan G.; Childs, Thomas E.; Grigsby, Kolter B.

2016-01-01

Key points Physical inactivity, which drastically increases with advancing age, is associated with numerous chronic diseases.The nucleus accumbens (the pleasure and reward ‘hub’ in the brain) influences wheel running behaviour in rodents.RNA‐sequencing and subsequent bioinformatics analysis led us to hypothesize a potential relationship between the regulation of dendritic spine density, the molecules involved in synaptic transmission, and age‐related reductions in wheel running. Upon completion of follow‐up studies, we developed the working model that synaptic plasticity in the nucleus accumbens is central to age‐related changes in voluntary running.Testing this hypothesis, inhibition of Cdk5 (comprising a molecule central to the processes described above) in the nucleus accumbens reduced wheel running.The results of the present study show that reductions in synaptic transmission and Cdk5 function are related to decreases in voluntary running behaviour and provide guidance for understanding the neural mechanisms that underlie age‐dependent reductions in the motivation to be physically active. Abstract Increases in age are often associated with reduced levels of physical activity, which, in turn, associates with the development of numerous chronic diseases. We aimed to assess molecular differences in the nucleus accumbens (NAc) (a specific brain nucleus postulated to influence rewarding behaviour) with respect to wheel running and sedentary female Wistar rats at 8 and 14 weeks of age. RNA‐sequencing was used to interrogate transcriptomic changes between 8‐ and 14‐week‐old wheel running rats, and select transcripts were later analysed by quantitative RT‐PCR in age‐matched sedentary rats. Voluntary wheel running was greatest at 8 weeks and had significantly decreased by 12 weeks. From 619 differentially expressed mRNAs, bioinformatics suggested that cAMP‐mediated signalling, dopamine‐ and cAMP‐regulated neuronal phosphoprotein of 32�

Maximal metabolic rates during voluntary exercise, forced exercise, and cold exposure in house mice selectively bred for high wheel-running.

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Rezende, Enrico L; Chappell, Mark A; Gomes, Fernando R; Malisch, Jessica L; Garland, Theodore

2005-06-01

Selective breeding for high wheel-running activity has generated four lines of laboratory house mice (S lines) that run about 170% more than their control counterparts (C lines) on a daily basis, mostly because they run faster. We tested whether maximum aerobic metabolic rates (V(O2max)) have evolved in concert with wheel-running, using 48 females from generation 35. Voluntary activity and metabolic rates were measured on days 5+6 of wheel access (mimicking conditions during selection), using wheels enclosed in metabolic chambers. Following this, V(O2max) was measured twice on a motorized treadmill and twice during cold-exposure in a heliox atmosphere (HeO2). Almost all measurements, except heliox V(O2max), were significantly repeatable. After accounting for differences in body mass (S running speeds on the treadmill. However, running speeds and V(O2max) during voluntary exercise were significantly higher in S lines. Nevertheless, S mice never voluntarily achieved the V(O2max) elicited during their forced treadmill trials, suggesting that aerobic capacity per se is not limiting the evolution of even higher wheel-running speeds in these lines. Our results support the hypothesis that S mice have genetically higher motivation for wheel-running and they demonstrate that behavior can sometimes evolve independently of performance capacities. We also discuss the possible importance of domestication as a confounding factor to extrapolate results from this animal model to natural populations.

Open-field behavior of house mice selectively bred for high voluntary wheel-running.

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Bronikowski, A M; Carter, P A; Swallow, J G; Girard, I A; Rhodes, J S; Garland, T

2001-05-01

Open-field behavioral assays are commonly used to test both locomotor activity and emotionality in rodents. We performed open-field tests on house mice (Mus domesticus) from four replicate lines genetically selected for high voluntary wheel-running for 22 generations and from four replicate random-bred control lines. Individual mice were recorded by video camera for 3 min in a 1-m2 open-field arena on 2 consecutive days. Mice from selected lines showed no statistical differences from control mice with respect to distance traveled, defecation, time spent in the interior, or average distance from the center of the arena during the trial. Thus, we found little evidence that open-field behavior, as traditionally defined, is genetically correlated with wheel-running behavior. This result is a useful converse test of classical studies that report no increased wheel-running in mice selected for increased open-field activity. However, mice from selected lines turned less in their travel paths than did control-line mice, and females from selected lines had slower travel times (longer latencies) to reach the wall. We discuss these results in the context of the historical open-field test and newly defined measures of open-field activity.

Serotonin-mediated central fatigue underlies increased endurance capacity in mice from lines selectively bred for high voluntary wheel running.

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Claghorn, Gerald C; Fonseca, Ivana A T; Thompson, Zoe; Barber, Curtis; Garland, Theodore

2016-07-01

Serotonin (5-hydroxytryptamine; 5-HT) is implicated in central fatigue, and 5-HT1A pharmaceuticals are known to influence locomotor endurance in both rodents and humans. We studied the effects of a 5-HT1A agonist and antagonist on both forced and voluntary exercise in the same set of mice. This cohort of mice was taken from 4 replicate lines of mice that have been selectively bred for high levels of voluntary wheel running (HR) as compared with 4 non-selected control (C) lines. HR mice run voluntarily on wheels about 3× as many revolutions per day as compared with C, and have greater endurance during forced treadmill exercise. We hypothesized that drugs targeting serotonin receptors would have differential effects on locomotor behavior of HR and C mice. Subcutaneous injections of a 5-HT1A antagonist (WAY-100,635), a combination of 5-HT1A agonist and a 5-HT1A/1B partial agonist (8-OH-DPAT+pindolol), or physiological saline were given to separate groups of male mice before the start of each of three treadmill trials. The same manipulations were used later during voluntary wheel running on three separate nights. WAY-100,635 decreased treadmill endurance in HR but not C mice (dose by linetype interaction, P=0.0014). 8-OH-DPAT+pindolol affected treadmill endurance (PWheel running was reduced in HR but not C mice at the highest dose of 8-OH-DPAT+pindolol (dose by linetype, P=0.0221), but was not affected by WAY-100,635 treatment. These results provide further evidence that serotonin signaling is an important determinant of performance during both forced and voluntary exercise. Although the elevated wheel running of HR mice does not appear related to alterations in serotonin signaling, their enhanced endurance capacity does. More generally, our results indicate that both forced and voluntary exercise can be affected by an intervention that acts (primarily) centrally. Copyright © 2016 Elsevier Inc. All rights reserved.

Voluntary wheel running increases bile acid as well as cholesterol excretion and decreases atherosclerosis in hypercholesterolemic mice

NARCIS (Netherlands)

Meissner, Maxi; Lombardo, Elisa; Havinga, Rick; Tietge, Uwe J. F.; Kuipers, Folkert; Groen, Albert K.

2011-01-01

Objective: Regular physical activity decreases the risk for atherosclerosis but underlying mechanisms are not fully understood. We questioned whether voluntary wheel running provokes specific modulations in cholesterol turnover that translate into a decreased atherosclerotic burden in

Effect of long-term voluntary exercise wheel running on susceptibility to bacterial pulmonary infections in a mouse model

DEFF Research Database (Denmark)

van de Weert-van Leeuwen, Pauline B; de Vrankrijker, Angélica M M; Fentz, Joachim

2013-01-01

moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa) load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should......Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim...... of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa) affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28...

Wheel running decreases the positive reinforcing effects of heroin.

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Smith, Mark A; Pitts, Elizabeth G

2012-01-01

The purpose of this study was to examine the effects of voluntary wheel running on the positive reinforcing effects of heroin in rats with an established history of drug self-administration. Rats were assigned to sedentary (no wheel) and exercise (wheel) conditions and trained to self-administer cocaine under positive reinforcement contingencies. Rats acquiring cocaine self-administration were then tested with various doses of heroin during daily test sessions. Sedentary rats self-administered more heroin than exercising rats, and this effect was greatest at low and moderate doses of heroin. These data suggest that voluntary wheel running decreases the positive reinforcing effects of heroin.

Nesting behavior of house mice (Mus domesticus) selected for increased wheel-running activity.

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Carter, P A; Swallow, J G; Davis, S J; Garland, T

2000-03-01

Nest building was measured in "active" (housed with access to running wheels) and "sedentary" (without wheel access) mice (Mus domesticus) from four replicate lines selected for 10 generations for high voluntary wheel-running behavior, and from four randombred control lines. Based on previous studies of mice bidirectionally selected for thermoregulatory nest building, it was hypothesized that nest building would show a negative correlated response to selection on wheel-running. Such a response could constrain the evolution of high voluntary activity because nesting has also been shown to be positively genetically correlated with successful production of weaned pups. With wheel access, selected mice of both sexes built significantly smaller nests than did control mice. Without wheel access, selected females also built significantly smaller nests than did control females, but only when body mass was excluded from the statistical model, suggesting that body mass mediated this correlated response to selection. Total distance run and mean running speed on wheels was significantly higher in selected mice than in controls, but no differences in amount of time spent running were measured, indicating a complex cause of the response of nesting to selection for voluntary wheel running.

Voluntary wheel running augments aortic l-arginine transport and endothelial function in rats with chronic kidney disease.

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Martens, Christopher R; Kuczmarski, James M; Kim, Jahyun; Guers, John J; Harris, M Brennan; Lennon-Edwards, Shannon; Edwards, David G

2014-08-15

Reduced nitric oxide (NO) synthesis contributes to risk for cardiovascular disease in chronic kidney disease (CKD). Vascular uptake of the NO precursor l-arginine (ARG) is attenuated in rodents with CKD, resulting in reduced substrate availability for NO synthesis and impaired vascular function. We tested the effect of 4 wk of voluntary wheel running (RUN) and/or ARG supplementation on endothelium-dependent relaxation (EDR) in rats with CKD. Twelve-week-old male Sprague-Dawley rats underwent ⅚ ablation infarction surgery to induce CKD, or SHAM surgery as a control. Beginning 4 wk following surgery, CKD animals either remained sedentary (SED) or received one of the following interventions: supplemental ARG, RUN, or combined RUN+ARG. Animals were euthanized 8 wk after surgery, and EDR was assessed. EDR was significantly impaired in SED vs. SHAM animals after 8 wk, in response to ACh (10(-9)-10(-5) M) as indicated by a reduced area under the curve (AUC; 44.56 ± 9.01 vs 100 ± 4.58, P RUN and RUN+ARG-treated animals. Maximal relaxation was elevated above SED in RUN+ARG animals only. l-[(3)H]arginine uptake was impaired in both SED and ARG animals and was improved in RUN and RUN+ARG animals. The results suggest that voluntary wheel running is an effective therapy to improve vascular function in CKD and may be more beneficial when combined with l-arginine. Copyright © 2014 the American Physiological Society.

Resting Is Rusting: A Critical View on Rodent Wheel-Running Behavior.

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Richter, Sophie Helene; Gass, Peter; Fuss, Johannes

2014-08-01

Physical exercise is known to exert various beneficial effects on brain function and bodily health throughout life. In biomedical research, these effects are widely studied by introducing running wheels into the cages of laboratory rodents. Yet, although rodents start to run in the wheels immediately, and perform wheel-running excessively on a voluntary basis, the biological significance of wheel-running is still not clear. Here, we review the current literature on wheel-running and discuss potentially negative side-effects that may give cause for concern. We particularly emphasize on analogies of wheel-running with stereotypic and addictive behavior to stimulate further research on this topic. © The Author(s) 2014.

Effects of size, sex, and voluntary running speeds on costs of locomotion in lines of laboratory mice selectively bred for high wheel-running activity.

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Rezende, Enrico L; Kelly, Scott A; Gomes, Fernando R; Chappell, Mark A; Garland, Theodore

2006-01-01

Selective breeding for over 35 generations has led to four replicate (S) lines of laboratory house mice (Mus domesticus) that run voluntarily on wheels about 170% more than four random-bred control (C) lines. We tested whether S lines have evolved higher running performance by increasing running economy (i.e., decreasing energy spent per unit of distance) as a correlated response to selection, using a recently developed method that allows for nearly continuous measurements of oxygen consumption (VO2) and running speed in freely behaving animals. We estimated slope (incremental cost of transport [COT]) and intercept for regressions of power (the dependent variable, VO2/min) on speed for 49 males and 47 females, as well as their maximum VO2 and speeds during wheel running, under conditions mimicking those that these lines face during the selection protocol. For comparison, we also measured COT and maximum aerobic capacity (VO2max) during forced exercise on a motorized treadmill. As in previous studies, the increased wheel running of S lines was mainly attributable to increased average speed, with males also showing a tendency for increased time spent running. On a whole-animal basis, combined analysis of males and females indicated that COT during voluntary wheel running was significantly lower in the S lines (one-tailed P=0.015). However, mice from S lines are significantly smaller and attain higher maximum speeds on the wheels; with either body mass or maximum speed (or both) entered as a covariate, the statistical significance of the difference in COT is lost (one-tailed P> or =0.2). Thus, both body size and behavior are key components of the reduction in COT. Several statistically significant sex differences were observed, including lower COT and higher resting metabolic rate in females. In addition, maximum voluntary running speeds were negatively correlated with COT in females but not in males. Moreover, males (but not females) from the S lines exhibited

Impact of wheel running on chronic ethanol intake in aged Syrian hamsters.

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Brager, Allison J; Hammer, Steven B

2012-10-10

Alcohol dependence in aging populations is seen as a public health concern, most recently because of the significant proportion of heavy drinking among "Baby Boomers." Basic animal research on the effects of aging on physiological and behavioral regulation of ethanol (EtOH) intake is sparse, since most of this research is limited to younger models of alcoholism. Here, EtOH drinking and preference were measured in groups of aged Syrian hamsters. Further, because voluntary exercise (wheel-running) is a rewarding substitute for EtOH in young adult hamsters, the potential for such reward substitution was also assessed. Aged (24 month-old) male hamsters were subjected to a three-stage regimen of free-choice EtOH (20% v/v) or water and unlocked or locked running wheels to investigate the modulatory effects of voluntary wheel running on EtOH intake and preference. Levels of fluid intake and activity were recorded daily across 60 days of experimentation. Prior to wheel running, levels of EtOH intake were significantly less than levels of water intake, resulting in a low preference for EtOH (30%). Hamsters with access to an unlocked running wheel had decreased EtOH intake and preference compared with hamsters with access to a locked running wheel. These group differences in EtOH intake and preference were sustained for up to 10 days after running wheels were re-locked. These results extend upon those of our previous work in young adult hamsters, indicating that aging dampens EtOH intake and preference. Voluntary wheel running further limited EtOH intake, suggesting that exercise could offer a practical approach for managing late-life alcoholism. Copyright © 2012 Elsevier Inc. All rights reserved.

Sex-Dependent and Independent Effects of Long-Term Voluntary Wheel Running on Bdnf mRNA and Protein Expression

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Venezia, Andrew C.; Guth, Lisa M.; Sapp, Ryan M.; Spangenburg, Espen E.; Roth, Stephen M.

2016-01-01

The beneficial effects of physical activity on brain health (synaptogenesis, neurogenesis, enhanced synaptic plasticity, improved learning and memory) appear to be mediated through changes in region-specific expression of neurotrophins, transcription factors, and postsynaptic receptors, though investigations of sex differences in response to long-term voluntary wheel running are limited.

Stereotypic wheel running decreases cortical activity in mice

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Fisher, Simon P.; Cui, Nanyi; McKillop, Laura E.; Gemignani, Jessica; Bannerman, David M.; Oliver, Peter L.; Peirson, Stuart N.; Vyazovskiy, Vladyslav V.

2016-01-01

Prolonged wakefulness is thought to gradually increase ‘sleep need' and influence subsequent sleep duration and intensity, but the role of specific waking behaviours remains unclear. Here we report the effect of voluntary wheel running during wakefulness on neuronal activity in the motor and somatosensory cortex in mice. We find that stereotypic wheel running is associated with a substantial reduction in firing rates among a large subpopulation of cortical neurons, especially at high speeds. Wheel running also has longer-term effects on spiking activity across periods of wakefulness. Specifically, cortical firing rates are significantly higher towards the end of a spontaneous prolonged waking period. However, this increase is abolished when wakefulness is dominated by running wheel activity. These findings indicate that wake-related changes in firing rates are determined not only by wake duration, but also by specific waking behaviours. PMID:27748455

Wheel-running activity modulates circadian organization and the daily rhythm of eating behavior

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Pendergast, Julie S.; Branecky, Katrina L.; Huang, Roya; Niswender, Kevin D.; Yamazaki, Shin

2014-01-01

Consumption of high-fat diet acutely alters the daily rhythm of eating behavior and circadian organization (the phase relationship between oscillators in central and peripheral tissues) in mice. Voluntary wheel-running activity counteracts the obesogenic effects of high-fat diet and also modulates circadian rhythms in mice. In this study, we sought to determine whether voluntary wheel-running activity could prevent the proximate effects of high-fat diet consumption on circadian organization and behavioral rhythms in mice. Mice were housed with locked or freely rotating running wheels and fed chow or high-fat diet for 1 week and rhythms of locomotor activity, eating behavior, and molecular timekeeping (PERIOD2::LUCIFERASE luminescence rhythms) in ex vivo tissues were measured. Wheel-running activity delayed the phase of the liver rhythm by 4 h in both chow- and high-fat diet-fed mice. The delayed liver phase was specific to wheel-running activity since an enriched environment without the running wheel did not alter the phase of the liver rhythm. In addition, wheel-running activity modulated the effect of high-fat diet consumption on the daily rhythm of eating behavior. While high-fat diet consumption caused eating events to be more evenly dispersed across the 24 h-day in both locked-wheel and wheel-running mice, the effect of high-fat diet was much less pronounced in wheel-running mice. Together these data demonstrate that wheel-running activity is a salient factor that modulates liver phase and eating behavior rhythms in both chow- and high-fat-diet fed mice. Wheel-running activity in mice is both a source of exercise and a self-motivating, rewarding behavior. Understanding the putative reward-related mechanisms whereby wheel-running activity alters circadian rhythms could have implications for human obesity since palatable food and exercise may modulate similar reward circuits. PMID:24624109

Effect of long-term voluntary exercise wheel running on susceptibility to bacterial pulmonary infections in a mouse model.

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Pauline B van de Weert-van Leeuwen

Full Text Available Regular moderate exercise has been suggested to exert anti-inflammatory effects and improve immune effector functions, resulting in reduced disease incidence and viral infection susceptibility. Whether regular exercise also affects bacterial infection susceptibility is unknown. The aim of this study was to investigate whether regular voluntary exercise wheel running prior to a pulmonary infection with bacteria (P. aeruginosa affects lung bacteriology, sickness severity and phagocyte immune function in mice. Balb/c mice were randomly placed in a cage with or without a running wheel. After 28 days, mice were intranasally infected with P. aeruginosa. Our study showed that regular exercise resulted in a higher sickness severity score and bacterial (P. aeruginosa loads in the lungs. The phagocytic capacity of monocytes and neutrophils from spleen and lungs was not affected. Although regular moderate exercise has many health benefits, healthy mice showed increased bacterial (P. aeruginosa load and symptoms, after regular voluntary exercise, with perseverance of the phagocytic capacity of monocytes and neutrophils. Whether patients, suffering from bacterial infectious diseases, should be encouraged to engage in exercise and physical activities with caution requires further research.

Changes in hippocampal theta rhythm and their correlations with speed during different phases of voluntary wheel running in rats.

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Li, J-Y; Kuo, T B J; Hsieh, I-T; Yang, C C H

2012-06-28

Hippocampal theta rhythm (4-12 Hz) can be observed during locomotor behavior, but findings on the relationship between locomotion speed and theta frequency are inconsistent if not contradictory. The inconsistency may be because of the difficulties that previous analyses and protocols have had excluding the effects of behavior training. We recorded the first or second voluntary wheel running each day, and assumed that theta frequency and activity are correlated with speed in different running phases. By simultaneously recording electroencephalography, physical activity, and wheel running speed, this experiment explored the theta oscillations during spontaneous running of the 12-h dark period. The recording was completely wireless and allowed the animal to run freely while being recorded in the wheel. Theta frequency and theta power of middle frequency were elevated before running and theta frequency, theta power of middle frequency, physical activity, and running speed maintained persistently high levels during running. The slopes of the theta frequency and theta activity (4-9.5 Hz) during the initial running were different compared to the same values during subsequent running. During the initial running, the running speed was positively correlated with theta frequency and with theta power of middle frequency. Over the 12-h dark period, the running speed did not positively correlate with theta frequency but was significantly correlated with theta power of middle frequency. Thus, theta frequency was associated with running speed only at the initiation of running. Furthermore, theta power of middle frequency was associated with speed and with physical activity during running when chronological order was not taken into consideration. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Voluntary running enhances glymphatic influx in awake behaving, young mice

DEFF Research Database (Denmark)

von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

2018-01-01

that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We...... of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas...

Mice selectively bred for high voluntary wheel-running behavior conserve more fat despite increased exercise.

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Hiramatsu, Layla; Garland, Theodore

2018-04-20

Physical activity is an important component of energy expenditure, and acute changes in activity can lead to energy imbalances that affect body composition, even under ad libitum food availability. One example of acute increases in physical activity is four replicate, selectively-bred High Runner (HR) lines of mice that voluntarily run ~3-fold more wheel revolutions per day over 6-day trials and are leaner, as compared with four non-selected control (C) lines. We expected that voluntary exercise would increase food consumption, build lean mass, and reduce fat mass, but that these effects would likely differ between HR and C lines or between the sexes. We compared wheel running, cage activity, food consumption, and body composition between HR and C lines for young adults of both sexes, and examined interrelationships of those traits across 6 days of wheel access. Before wheel testing, HR mice weighed less than C, primarily due to reduced lean mass, and females were lighter than males, entirely due to lower lean mass. Over 6 days of wheel access, all groups tended to gain small amounts of lean mass, but lose fat mass. HR mice lost less fat than C mice, in spite of much higher activity levels, resulting in convergence to a fat mass of ~1.7 g for all 4 groups. HR mice consumed more food than C mice (with body mass as a covariate), even accounting for their higher activity levels. No significant sex-by-linetype interactions were observed for any of the foregoing traits. Structural equation models showed that the four sex-by-linetype groups differed considerably in the complex phenotypic architecture of these traits. Interrelationships among traits differed by genetic background and sex, lending support to the idea that recommendations regarding weight management, diet, and exercise may need to be tailored to the individual level. Copyright © 2018 Elsevier Inc. All rights reserved.

Dopamine D1 receptor modulation in nucleus accumbens lowers voluntary wheel running in rats bred to run high distances.

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Roberts, Michael D; Gilpin, Leigh; Parker, Kyle E; Childs, Thomas E; Will, Matthew J; Booth, Frank W

2012-02-01

Dopamine signaling in the nucleus accumbens (NAc) has been postulated to influence reward development towards drugs of abuse and exercise. Herein, we used generation 4-5 rats that were selectively bred to voluntary run high (HVR) versus low (LVR) distances in order to examine if dopamine-like 1 (D1) receptor modulation in the NAc differentially affects nightly voluntary wheel running between these lines. A subset of generation 5-6 HVR and LVR rats were also used to study the mRNA expression of key genes related to reward and addiction in the NAc (i.e., DRD1, DRD5, DRD2, Nr4a2, FosB, and BDNF). In a crossover fashion, a D1-like agonist SKF 82958 (2 μg per side) or D1-like full antagonist SCH 23390 (4 μg per side) was bilaterally injected into the NAc of HVR and LVR female Wistar rats prior to their high running nights. Notably, during hours 2-4 (between 2000 and 2300) of the dark cycle there was a significant decrement in running distances in the HVR rats treated with the D1 agonist (p=0.025) and antagonist (p=0.017) whereas the running distances in LVR rats were not affected. Interestingly, HVR and LVR rats possessed similar NAc concentrations of the studied mRNAs. These data suggest that: a) animals predisposed to run high distances on a nightly basis may quickly develop a rewarding response to exercise due to an optimal D1-like receptor signaling pathway in the NAc that can be perturbed by either activation or blocking, b) D1-like agonist or antagonist injections do not increase running distances in rats that are bred to run low nightly distances, and c) running differences between HVR and LVR animals are seemingly not due to the expression of the studied mRNAs. Given the societal prevalence of obesity and extraneous physical inactivity, future studies should be performed in order to further determine the culprit for the low running phenotype observed in LVR animals. Copyright © 2011. Published by Elsevier Inc.

Rapid Alterations in Perirenal Adipose Tissue Transcriptomic Networks with Cessation of Voluntary Running.

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Gregory N Ruegsegger

Full Text Available In maturing rats, the growth of abdominal fat is attenuated by voluntary wheel running. After the cessation of running by wheel locking, a rapid increase in adipose tissue growth to a size that is similar to rats that have never run (i.e. catch-up growth has been previously reported by our lab. In contrast, diet-induced increases in adiposity have a slower onset with relatively delayed transcriptomic responses. The purpose of the present study was to identify molecular pathways associated with the rapid increase in adipose tissue after ending 6 wks of voluntary running at the time of puberty. Age-matched, male Wistar rats were given access to running wheels from 4 to 10 weeks of age. From the 10th to 11th week of age, one group of rats had continued wheel access, while the other group had one week of wheel locking. Perirenal adipose tissue was extracted, RNA sequencing was performed, and bioinformatics analyses were executed using Ingenuity Pathway Analysis (IPA. IPA was chosen to assist in the understanding of complex 'omics data by integrating data into networks and pathways. Wheel locked rats gained significantly more fat mass and significantly increased body fat percentage between weeks 10-11 despite having decreased food intake, as compared to rats with continued wheel access. IPA identified 646 known transcripts differentially expressed (p < 0.05 between continued wheel access and wheel locking. In wheel locked rats, IPA revealed enrichment of transcripts for the following functions: extracellular matrix, macrophage infiltration, immunity, and pro-inflammatory. These findings suggest that increases in visceral adipose tissue that accompanies the cessation of pubertal physical activity are associated with the alteration of multiple pathways, some of which may potentiate the development of pubertal obesity and obesity-associated systemic low-grade inflammation that occurs later in life.

Maternal exposure to Western diet affects adult body composition and voluntary wheel running in a genotype-specific manner in mice.

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Hiramatsu, Layla; Kay, Jarren C; Thompson, Zoe; Singleton, Jennifer M; Claghorn, Gerald C; Albuquerque, Ralph L; Ho, Brittany; Ho, Brett; Sanchez, Gabriela; Garland, Theodore

2017-10-01

Some human diseases, including obesity, Type II diabetes, and numerous cancers, are thought to be influenced by environments experienced in early life, including in utero. Maternal diet during the perinatal period may be especially important for adult offspring energy balance, potentially affecting both body composition and physical activity. This effect may be mediated by the genetic background of individuals, including, for example, potential "protective" mechanisms for individuals with inherently high levels of physical activity or high basal metabolic rates. To examine some of the genetic and environmental factors that influence adult activity levels, we used an ongoing selection experiment with 4 replicate lines of mice bred for high voluntary wheel running (HR) and 4 replicate, non-selected control lines (C). Dams (half HR and half C) were fed a "Western" diet (WD, high in fat and sucrose) or a standard diet (SD) from 2weeks prior to mating until their pups could feed on solid food (14days of age). We analyzed dam and litter characteristics from birth to weaning, and offspring mass and physical activity into adulthood. One male offspring from each litter received additional metabolic and behavioral tests. Maternal WD caused pups to eat solid food significantly earlier for C litters, but not for HR litters (interaction of maternal environment and genotype). With dam mass as a covariate, mean pup mass was increased by maternal WD but litter size was unaffected. HR dams had larger litters and tended to have smaller pups than C dams. Home-cage activity of juvenile focal males was increased by maternal WD. Juvenile lean mass, fat mass, and fat percent were also increased by maternal WD, but food consumption (with body mass as a covariate) was unaffected (measured only for focal males). Behavior in an elevated plus maze, often used to indicate anxiety, was unaffected by maternal WD. Maximal aerobic capacity (VO 2 max) was also unaffected by maternal WD, but HR had

Behavioral Traits are Affected by Selective Breeding for Increased Wheel-Running Behavior in Mice

NARCIS (Netherlands)

Jonas, I.; Schubert, K. A.; Reijne, A. C.; Scholte, J.; Garland, T.; Gerkema, M. P.; Scheurink, A. J. W.; Nyakas, C.; van Dijk, G.; Garland Jr., T.; Maxson, Stephen

Voluntary physical activity may be related to personality traits. Here, we investigated these relations in two mouse lines selectively bred for high voluntary wheel-running behavior and in one non-selected control line. Selection lines were more explorative and "information gathering" in the

Running wheel exercise enhances recovery from nigrostriatal dopamine injury without inducing neuroprotection.

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O'Dell, S J; Gross, N B; Fricks, A N; Casiano, B D; Nguyen, T B; Marshall, J F

2007-02-09

Forced use of the forelimb contralateral to a unilateral injection of the dopaminergic neurotoxin 6-hydroxydopamine can promote recovery of motor function in that limb and can significantly decrease damage to dopamine terminals. The present study was conducted to determine (1) whether a form of voluntary exercise, wheel running, would improve motor performance in rats with such lesions, and (2) whether any beneficial effects of wheel running are attributable to ameliorating the dopaminergic damage. In experiment 1, rats were allowed to run in exercise wheels or kept in home cages for 2 1/2 weeks, then given stereotaxic infusions of 6-hydroxydopamine into the left striatum. The rats were replaced into their original environments (wheels or home cages) for four additional weeks, and asymmetries in forelimb use were quantified at 3, 10, 17, and 24 days postoperatively. After killing, dopaminergic damage was assessed by both quantifying 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid methyl ester ([(125)I]RTI-55) binding to striatal dopamine transporters and counting tyrosine hydroxylase-positive cells in the substantia nigra. Exercised 6-hydroxydopamine-infused rats showed improved motor outcomes relative to sedentary lesioned controls, effects that were most apparent at postoperative days 17 and 24. Despite this behavioral improvement, 6-hydroxydopamine-induced loss of striatal dopamine transporters and tyrosine hydroxylase-positive nigral cells in exercised and sedentary groups did not differ. Since prior studies suggested that forced limb use improves motor performance by sparing nigrostriatal dopaminergic neurons from 6-hydroxydopamine damage, experiment 2 used a combined regimen of forced plus voluntary wheel running. Again, we found that the motor performance of exercised rats improved more rapidly than that of sedentary controls, but that there were no differences between these groups in the damage produced by 6-hydroxydopamine. It appears that voluntary

Voluntary resistance running induces increased hippocampal neurogenesis in rats comparable to load-free running.

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Lee, Min Chul; Inoue, Koshiro; Okamoto, Masahiro; Liu, Yu Fan; Matsui, Takashi; Yook, Jang Soo; Soya, Hideaki

2013-03-14

Recently, we reported that voluntary resistance wheel running with a resistance of 30% of body weight (RWR), which produces shorter distances but higher work levels, enhances spatial memory associated with hippocampal brain-derived neurotrophic factor (BDNF) signaling compared to wheel running without a load (WR) [17]. We thus hypothesized that RWR promotes adult hippocampal neurogenesis (AHN) as a neuronal substrate underlying this memory improvement. Here we used 10-week-old male Wistar rats divided randomly into sedentary (Sed), WR, and RWR groups. All rats were injected intraperitoneally with the thymidine analogue 5-Bromo-2'-deoxuridine (BrdU) for 3 consecutive days before wheel running. We found that even when the average running distance decreased by about half, the average work levels significantly increased in the RWR group, which caused muscular adaptation (oxidative capacity) for fast-twitch plantaris muscle without causing any negative stress effects. Additionally, immunohistochemistry revealed that the total BrdU-positive cells and newborn mature cells (BrdU/NeuN double-positive) in the dentate gyrus increased in both the WR and RWR groups. These results provide new evidence that RWR has beneficial effects on AHN comparable to WR, even with short running distances. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Voluntary running enhances glymphatic influx in awake behaving, young mice.

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von Holstein-Rathlou, Stephanie; Petersen, Nicolas Caesar; Nedergaard, Maiken

2018-01-01

Vascular pathology and protein accumulation contribute to cognitive decline, whereas exercise can slow vascular degeneration and improve cognitive function. Recent investigations suggest that glymphatic clearance measured in aged mice while anesthetized is enhanced following exercise. We predicted that exercise would also stimulate glymphatic activity in awake, young mice with higher baseline glymphatic function. Therefore, we assessed glymphatic function in young female C57BL/6J mice following five weeks voluntary wheel running and in sedentary mice. The active mice ran a mean distance of 6km daily. We injected fluorescent tracers in cisterna magna of awake behaving mice and in ketamine/xylazine anesthetized mice, and later assessed tracer distribution in coronal brain sections. Voluntary exercise consistently increased CSF influx during wakefulness, primarily in the hypothalamus and ventral parts of the cortex, but also in the middle cerebral artery territory. While glymphatic activity was higher under ketamine/xylazine anesthesia, we saw a decrease in glymphatic function during running in awake mice after five weeks of wheel running. In summary, daily running increases CSF flux in widespread areas of the mouse brain, which may contribute to the pro-cognitive effects of exercise. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

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Timonen Jussi

2011-01-01

Full Text Available Abstract Background Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT together with peripheral quantitative computed tomography (pQCT to examine the microstructure of the distal femoral metaphysis in mice. Methods Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C, control + running (CR, high-fat diet (HF, and high-fat diet + running (HFR. After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and μCT measurements. Results The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR, with increased epididymal fat pad mass and impaired insulin sensitivity. These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia. Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure. Conclusions The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth

A comparison of two types of running wheel in terms of mouse preference, health, and welfare.

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Walker, Michael; Mason, Georgia

2018-07-01

Voluntary wheel running occurs in mice of all strains, sexes, and ages. Mice find voluntary wheel running rewarding, and it leads to numerous health benefits. For this reason wheels are used both to enhance welfare and to create models of exercise. However, many designs of running wheel are used. This makes between-study comparisons difficult, as this variability could potentially affect the amount, pattern, and/or intensity of running behaviour, and thence the wheels' effects on welfare and exercise-related changes in anatomy and physiology. This study therefore evaluated two commercially available models, chosen because safe for group-housed mice: Bio Serv®'s "fast-trac" wheel combo and Ware Manufacturing Inc.'s stainless steel mesh 5″ upright wheel. Working with a total of three hundred and fifty one female C57BL/6, DBA/2 and BALB/c mice, we assessed these wheels' relative utilization by mice when access was free; the strength of motivation for each wheel-type when access required crossing an electrified grid; and the impact each wheel had on mouse well-being (inferred from acoustic startle responses and neophobia) and exercise-related anatomical changes (BMI; heart and hind limb masses). Mice ran more on the "fast-trac" wheel regardless of whether both wheel-types were available at once, or only if one was present. In terms of motivation, subjects required to work to access a single wheel worked equally hard for both wheel-types (even if locked and thus not useable for running), but if provided with one working wheel for free and the other type of wheel (again unlocked) accessible via crossing the electrified grid, the "fast-trac" wheel emerged as more motivating, as the Maximum Price Paid for the Ware metal wheel was lower than that paid for the "fast-trac" plastic wheel, at least for C57BL/6s and DBA/2s. No deleterious consequences were noted with either wheel in terms of health and welfare, but only mice with plastic wheels developed significantly larger

Restricted vs. unrestricted wheel running in mice: Effects on brain, behavior and endocannabinoids.

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Biedermann, Sarah V; Auer, Matthias K; Bindila, Laura; Ende, Gabriele; Lutz, Beat; Weber-Fahr, Wolfgang; Gass, Peter; Fuss, Johannes

2016-11-01

Beneficial effects of voluntary wheel running on hippocampal neurogenesis, morphology and hippocampal-dependent behavior have widely been studied in rodents, but also serious side effects and similarities to stereotypy have been reported. Some mouse strains run excessively when equipped with running wheels, complicating the comparability to human exercise regimes. Here, we investigated how exercise restriction to 6h/day affects hippocampal morphology and metabolism, stereotypic and basal behaviors, as well as the endocannabinoid system in wheel running C57BL/6 mice; the strain most commonly used for behavioral analyses and psychiatric disease models. Restricted and unrestricted wheel running had similar effects on immature hippocampal neuron numbers, thermoregulatory nest building and basal home-cage behaviors. Surprisingly, hippocampal gray matter volume, assessed with magnetic resonance (MR) imaging at 9.4 Tesla, was only increased in unrestricted but not in restricted runners. Moreover, unrestricted runners showed less stereotypic behavior than restricted runners did. However, after blockage of running wheels for 24h stereotypic behavior also increased in unrestricted runners, arguing against a long-term effect of wheel running on stereotypic behavior. Stereotypic behaviors correlated with frontal glutamate and glucose levels assessed by 1 H-MR spectroscopy. While acute running increased plasma levels of the endocannabinoid anandamide in former studies in mice and humans, we found an inverse correlation of anandamide with the daily running distance after long-term running. In conclusion, although there are some diverging effects of restricted and unrestricted running on brain and behavior, restricted running does not per se seem to be a better animal model for aerobic exercise in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

Dopamine D3 receptor status modulates sexual dimorphism in voluntary wheel running behavior in mice.

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Klinker, Florian; Ko Hnemann, Kathrin; Paulus, Walter; Liebetanz, David

2017-08-30

Sexual dimorphism has been described in various aspects of physiological and pathophysiological processes involving dopaminergic signaling. This might account for the different disease characteristics in men and women in e.g. Parkinson's disease or ADHD. A better understanding might contribute to the future individualization of therapy. We examined spontaneous wheel running activity of male and female mice, homo- and heterozygote for dopamine D3 receptor deficiency (D3R -/- and D3R+/-), and compared them to wild type controls. We found higher wheel running activity in female mice than in their male littermates. D3-/- mice, irrespective of sex, were also hyperactive compared to both D3+/- and wild type animals. Hyperactivity of D3-/- female mice was pronounced during the first days of wheel running but then decreased while their male counterparts continued to be hyperactive. Physical activity was menstrual cycle-dependent. Activity fluctuations were also seen in D3 receptor knockout mice and are therefore presumably independent of D3 receptor activation. Our data underscore the complex interaction of dopaminergic signaling and gonadal hormones that leads to specific running behavior. Furthermore, we detected sex- and D3 receptor status-specific reactions during novel exposure to the running wheel. These findings suggest the need for adapting dopaminergic therapies to individual factors such as sex or even menstrual cycle to optimize therapeutic success. Copyright © 2017 Elsevier B.V. All rights reserved.

Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

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Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

2014-01-01

We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

Using wheel availability to shape running behavior of the rat towards improved behavioral and neurobiological outcomes.

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Basso, Julia C; Morrell, Joan I

2017-10-01

Though voluntary wheel running (VWR) has been used extensively to induce changes in both behavior and biology, little attention has been given to the way in which different variables influence VWR. This lack of understanding has led to an inability to utilize this behavior to its full potential, possibly blunting its effects on the endpoints of interest. We tested how running experience, sex, gonadal hormones, and wheel apparatus influence VWR in a range of wheel access "doses". VWR increases over several weeks, with females eventually running 1.5 times farther and faster than males. Limiting wheel access can be used as a tool to motivate subjects to run but restricts maximal running speeds attained by the rodents. Additionally, circulating gonadal hormones regulate wheel running behavior, but are not the sole basis of sex differences in running. Limitations from previous studies include the predominate use of males, emphasis on distance run, variable amounts of wheel availability, variable light-dark cycles, and possible food and/or water deprivation. We designed a comprehensive set of experiments to address these inconsistencies, providing data regarding the "microfeatures" of running, including distance run, time spent running, running rate, bouting behavior, and daily running patterns. By systematically altering wheel access, VWR behavior can be finely tuned - a feature that we hypothesize is due to its positive incentive salience. We demonstrate how to maximize VWR, which will allow investigators to optimize exercise-induced changes in their behavioral and/or biological endpoints of interest. Published by Elsevier B.V.

High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

Science.gov (United States)

Vellers, Heather L.; Letsinger, Ayland C.; Walker, Nicholas R.; Granados, Jorge Z.; Lightfoot, J. Timothy

2017-01-01

Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s) may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels. Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD) or high fat/high sugar (HFHS) diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males) and 17β-estradiol (females) to determine if sex hormone augmentation altered diet-induced changes in activity. Results: 117 mice (56♂, 61♀) were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p running-wheel distance in male (p = 0.05, 70 ± 28%) and female mice (p = 0.02, 57 ± 26%). In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat. Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones. PMID:28890701

Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling.

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Lee, Min Chul; Okamoto, Masahiro; Liu, Yu Fan; Inoue, Koshiro; Matsui, Takashi; Nogami, Haruo; Soya, Hideaki

2012-10-15

Although voluntary running has beneficial effects on hippocampal cognitive functions if done abundantly, it is still uncertain whether resistance running would be the same. For this purpose, voluntary resistance wheel running (RWR) with a load is a suitable model, since it allows increased work levels and resultant muscular adaptation in fast-twitch muscle. Here, we examined whether RWR would have potential effects on hippocampal cognitive functions with enhanced hippocampal brain-derived neurotrophic factor (BDNF), as does wheel running without a load (WR). Ten-week-old male Wistar rats were assigned randomly to sedentary (Sed), WR, and RWR (to a maximum load of 30% of body weight) groups for 4 wk. We found that in RWR, work levels increased with load, but running distance decreased by about half, which elicited muscular adaptation for fast-twitch plantaris muscle without causing any negative stress effects. Both RWR and WR led to improved spatial learning and memory as well as gene expressions of hippocampal BDNF signaling-related molecules. RWR increased hippocampal BDNF, tyrosine-related kinase B (TrkB), and cAMP response element-binding (CREB) protein levels, whereas WR increased only BDNF. With both exercise groups, there were correlations between spatial memory and BDNF protein (r = 0.41), p-CREB protein (r = 0.44), and work levels (r = 0.77). These results suggest that RWR plays a beneficial role in hippocampus-related cognitive functions associated with hippocampal BDNF signaling, even with short distances, and that work levels rather than running distance are more determinant of exercise-induced beneficial effects in wheel running with and without a load.

Voluntary wheel running reverses age-induced changes in hippocampal gene expression.

Directory of Open Access Journals (Sweden)

Rachel A Kohman

Full Text Available Normal aging alters expression of numerous genes within the brain. Some of these transcription changes likely contribute to age-associated cognitive decline, reduced neural plasticity, and the higher incidence of neuropathology. Identifying factors that modulate brain aging is crucial for improving quality of life. One promising intervention to counteract negative effects of aging is aerobic exercise. Aged subjects that exercise show enhanced cognitive performance and increased hippocampal neurogenesis and synaptic plasticity. Currently, the mechanisms behind the anti-aging effects of exercise are not understood. The present study conducted a microarray on whole hippocampal samples from adult (3.5-month-old and aged (18-month-old male BALB/c mice that were individually housed with or without running wheels for 8 weeks. Results showed that aging altered genes related to chromatin remodeling, cell growth, immune activity, and synapse organization compared to adult mice. Exercise was found to modulate many of the genes altered by aging, but in the opposite direction. For example, wheel running increased expression of genes related to cell growth and attenuated expression of genes involved in immune function and chromatin remodeling. Collectively, findings show that even late-onset exercise may attenuate age-related changes in gene expression and identifies possible pathways through which exercise may exert its beneficial effects.

Habituation contributes to the decline in wheel running within wheel-running reinforcement periods.

Science.gov (United States)

Belke, Terry W; McLaughlin, Ryan J

2005-02-28

Habituation appears to play a role in the decline in wheel running within an interval. Aoyama and McSweeney [Aoyama, K., McSweeney, F.K., 2001. Habituation contributes to within-session changes in free wheel running. J. Exp. Anal. Behav. 76, 289-302] showed that when a novel stimulus was presented during a 30-min interval, wheel-running rates following the stimulus increased to levels approximating those earlier in the interval. The present study sought to assess the role of habituation in the decline in running that occurs over a briefer interval. In two experiments, rats responded on fixed-interval 30-s schedules for the opportunity to run for 45 s. Forty reinforcers were completed in each session. In the first experiment, the brake and chamber lights were repeatedly activated and inactivated after 25 s of a reinforcement interval had elapsed to assess the effect on running within the remaining 20 s. Presentations of the brake/light stimulus occurred during nine randomly determined reinforcement intervals in a session. In the second experiment, a 110 dB tone was emitted after 25 s of the reinforcement interval. In both experiments, presentation of the stimulus produced an immediate decline in running that dissipated over sessions. No increase in running following the stimulus was observed in the first experiment until the stimulus-induced decline dissipated. In the second experiment, increases in running were observed following the tone in the first session as well as when data were averaged over several sessions. In general, the results concur with the assertion that habituation plays a role in the decline in wheel running that occurs within both long and short intervals. (c) 2004 Elsevier B.V. All rights reserved.

Responding for sucrose and wheel-running reinforcement: effect of pre-running.

Science.gov (United States)

Belke, Terry W

2006-01-10

Six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. To assess the effect of pre-running, animals were allowed to run for 1h prior to a session of responding for sucrose and running. Results showed that, after pre-running, response rates in the later segments of the 30-s schedule decreased in the presence of a wheel-running stimulus and increased in the presence of a sucrose stimulus. Wheel-running rates were not affected. Analysis of mean post-reinforcement pauses (PRP) broken down by transitions between successive reinforcers revealed that pre-running lengthened pausing in the presence of the stimulus signaling wheel running and shortened pauses in the presence of the stimulus signaling sucrose. No effect was observed on local response rates. Changes in pausing in the presence of stimuli signaling the two reinforcers were consistent with a decrease in the reinforcing efficacy of wheel running and an increase in the reinforcing efficacy of sucrose. Pre-running decreased motivation to respond for running, but increased motivation to work for food.

Long-Term Oral Feeding of Lutein-Fortified Milk Increases Voluntary Running Distance in Rats

OpenAIRE

Matsumoto, Megumi; Hagio, Masahito; Inoue, Ryo; Mitani, Tomohiro; Yajima, Masako; Hara, Hiroshi; Yajima, Takaji

2014-01-01

To evaluate the effects of lutein-fortified milk administration on running exercise, a voluntary wheel-running model was performed in rats. Four-week-old F344 rats were administered test milk (10 mL/kg) daily following a 4-h fasting period, and their running distances were measured each day for a 9-week period. Total weekly running distance significantly increased from the sixth week until the end of the test period in lutein-supplemented rats (lutein-fortified milk administered) compared wit...

Beneficial effects of fluoxetine, reboxetine, venlafaxine, and voluntary running exercise in stressed male rats with anxiety- and depression-like behaviors.

Science.gov (United States)

Lapmanee, Sarawut; Charoenphandhu, Jantarima; Charoenphandhu, Narattaphol

2013-08-01

Rodents exposed to mild but repetitive stress may develop anxiety- and depression-like behaviors. Whether this stress response could be alleviated by pharmacological treatments or exercise interventions, such as wheel running, was unknown. Herein, we determined anxiety- and depression-like behaviors in restraint stressed rats (2h/day, 5 days/week for 4 weeks) subjected to acute diazepam treatment (30min prior to behavioral test), chronic treatment with fluoxetine, reboxetine or venlafaxine (10mg/kg/day for 4 weeks), and/or 4-week voluntary wheel running. In elevated plus-maze (EPM) and forced swimming tests (FST), stressed rats spent less time in the open arms and had less swimming duration than the control rats, respectively, indicating the presence of anxiety- and depression-like behaviors. Stressed rats also developed learned fear as evaluated by elevated T-maze test (ETM). Although wheel running could reduce anxiety-like behaviors in both EPM and ETM, only diazepam was effective in the EPM, while fluoxetine, reboxetine, and venlafaxine were effective in the ETM. Fluoxetine, reboxetine, and wheel running, but not diazepam and venlafaxine, also reduced depression-like behavior in FST. Combined pharmacological treatment and exercise did not further reduce anxiety-like behavior in stressed rats. However, stressed rats treated with wheel running plus reboxetine or venlafaxine showed an increase in climbing duration in FST. In conclusion, regular exercise (voluntary wheel running) and pharmacological treatments, especially fluoxetine and reboxetine, could alleviate anxiety- and depression-like behaviors in stressed male rats. Copyright © 2013 Elsevier B.V. All rights reserved.

High Fat High Sugar Diet Reduces Voluntary Wheel Running in Mice Independent of Sex Hormone Involvement

Directory of Open Access Journals (Sweden)

Heather L. Vellers

2017-08-01

Full Text Available Introduction: Indirect results in humans suggest that chronic overfeeding decreases physical activity with few suggestions regarding what mechanism(s may link overfeeding and decreased activity. The primary sex hormones are known regulators of activity and there are reports that chronic overfeeding alters sex hormone levels. Thepurpose of this study was to determine if chronic overfeeding altered wheel running through altered sex hormone levels.Materials and Methods: C57BL/6J mice were bred and the pups were weaned at 3-weeks of age and randomly assigned to either a control (CFD or high fat/high sugar (HFHS diet for 9–11 weeks depending on activity analysis. Nutritional intake, body composition, sex hormone levels, and 3-day and 2-week wheel-running activity were measured. Additionally, groups of HFHS animals were supplemented with testosterone (males and 17β-estradiol (females to determine if sex hormone augmentation altered diet-induced changes in activity.Results: 117 mice (56♂, 61♀ were analyzed. The HFHS mice consumed significantly more calories per day than CFD mice (male: p < 0.0001; female: p < 0.0001 and had significantly higher body fat (male: p < 0.0001; female: p < 0.0001. The HFHS diet did not reduce sex hormone levels, but did significantly reduce acute running-wheel distance in male (p = 0.05, 70 ± 28% and female mice (p = 0.02, 57 ± 26%. In animals that received hormone supplementation, there was no significant effect on activity levels. Two-weeks of wheel access was not sufficient to alter HFHS-induced reductions in activity or increases in body fat.Conclusion: Chronic overfeeding reduces wheel running, but is independent of the primary sex hormones.

Acute Restraint Stress Alters Wheel-Running Behavior Immediately Following Stress and up to 20 Hours Later in House Mice.

Science.gov (United States)

Malisch, Jessica L; deWolski, Karen; Meek, Thomas H; Acosta, Wendy; Middleton, Kevin M; Crino, Ondi L; Garland, Theodore

In vertebrates, acute stressors-although short in duration-can influence physiology and behavior over a longer time course, which might have important ramifications under natural conditions. In laboratory rats, for example, acute stress has been shown to increase anxiogenic behaviors for days after a stressor. In this study, we quantified voluntary wheel-running behavior for 22 h following a restraint stress and glucocorticoid levels 24 h postrestraint. We utilized mice from four replicate lines that have been selectively bred for high voluntary wheel-running activity (HR mice) for 60 generations and their nonselected control (C) lines to examine potential interactions between exercise propensity and sensitivity to stress. Following 6 d of wheel access on a 12L∶12D photo cycle (0700-1900 hours, as during the routine selective breeding protocol), 80 mice were physically restrained for 40 min, beginning at 1400 hours, while another 80 were left undisturbed. Relative to unrestrained mice, wheel running increased for both HR and C mice during the first hour postrestraint (P Wheel running was also examined at four distinct phases of the photoperiod. Running in the period of 1600-1840 hours was unaffected by restraint stress and did not differ statistically between HR and C mice. During the period of peak wheel running (1920-0140 hours), restrained mice tended to run fewer revolutions (-11%; two-tailed P = 0.0733), while HR mice ran 473% more than C (P = 0.0008), with no restraint × line type interaction. Wheel running declined for all mice in the latter part of the scotophase (0140-0600 hours), restraint had no statistical effect on wheel running, but HR again ran more than C (+467%; P = 0.0122). Finally, during the start of the photophase (0720-1200 hours), restraint increased running by an average of 53% (P = 0.0443) in both line types, but HR and C mice did not differ statistically. Mice from HR lines had statistically higher plasma corticosterone concentrations

Stabilization of the wheel running phenotype in mice.

Science.gov (United States)

Bowen, Robert S; Cates, Brittany E; Combs, Eric B; Dillard, Bryce M; Epting, Jessica T; Foster, Brittany R; Patterson, Shawnee V; Spivey, Thomas P

2016-03-01

Increased physical activity is well known to improve health and wellness by modifying the risks for many chronic diseases. Rodent wheel running behavior is a beneficial surrogate model to evaluate the biology of daily physical activity in humans. Upon initial exposure to a running wheel, individual mice differentially respond to the experience, which confounds the normal activity patterns exhibited in this otherwise repeatable phenotype. To promote phenotypic stability, a minimum seven-day (or greater) acclimation period is utilized. Although phenotypic stabilization is achieved during this 7-day period, data to support acclimation periods of this length are not currently available in the literature. The purpose of this project is to evaluate the wheel running response in C57BL/6j mice immediately following exposure to a running wheel. Twenty-eight male and thirty female C57BL/6j mice (Jackson Laboratory, Bar Harbor, ME) were acquired at eight weeks of age and were housed individually with free access to running wheels. Wheel running distance (km), duration (min), and speed (m∙min(-1)) were measured daily for fourteen days following initial housing. One-way ANOVAs were used to evaluate day-to-day differences in each wheel running character. Limits of agreement and mean difference statistics were calculated between days 1-13 (acclimating) and day 14 (acclimated) to assess day-to-day agreement between each parameter. Wheel running distance (males: F=5.653, p=2.14 × 10(-9); females: F=8.217, p=1.20 × 10(-14)), duration (males: F=2.613, p=0.001; females: F=4.529, p=3.28 × 10(-7)), and speed (males: F=7.803, p=1.22 × 10(-13); females: F=13.140, p=2.00 × 10(-16)) exhibited day-to-day differences. Tukey's HSD post-hoc testing indicated differences between early (males: days 1-3; females: days 1-6) and later (males: days >3; females: days >6) wheel running periods in distance and speed. Duration only exhibited an anomalous difference between wheel running on day 13

Pre-exposure to wheel running disrupts taste aversion conditioning.

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Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2002-05-01

When rats are given access to a running wheel after drinking a flavored solution, they subsequently drink less of that flavor solution. It has been suggested that running produces a conditioned taste aversion (CTA). This study explored whether CTA is eliminated by prior exposure to wheel running [i.e., unconditioned stimulus (UCS) pre-exposure effect]. The rats in the experimental group (UW) were allowed to wheel run for 1 h daily for seven consecutive days of pre-exposure. Rats in the two other groups had either access to locked wheels (LW group) or were maintained in their home cages (HC group) during the pre-exposure days. All rats were then exposed to four paired and four unpaired trials using a "ABBAABBA" design. Conditioning trials were composed of one flavored liquid followed by 60-min access to wheel running. For the unpaired trials, rats received a different flavor not followed by the opportunity to run. All rats were then initially tested for water consumption followed by tests of the two flavors (paired or unpaired) in a counterbalanced design. Rats in the UW group show no CTA to the liquid paired with wheel running, whereas LW and HC groups developed CTA. These results indicate that pre-exposure to wheel running (i.e., the UCS), eliminates subsequent CTA.

Responding for sucrose and wheel-running reinforcement: effects of sucrose concentration and wheel-running reinforcer duration.

Science.gov (United States)

Belke, Terry W; Hancock, Stephanie D

2003-03-01

Six male albino rats were placed in running wheels and exposed to a fixed-interval 30-s schedule of lever pressing that produced either a drop of sucrose solution or the opportunity to run for a fixed duration as reinforcers. Each reinforcer type was signaled by a different stimulus. In Experiment 1, the duration of running was held constant at 15 s while the concentration of sucrose solution was varied across values of 0, 2.5. 5, 10, and 15%. As concentration decreased, postreinforcement pause duration increased and local rates decreased in the presence of the stimulus signaling sucrose. Consequently, the difference between responding in the presence of stimuli signaling wheel-running and sucrose reinforcers diminished, and at 2.5%, response functions for the two reinforcers were similar. In Experiment 2, the concentration of sucrose solution was held constant at 15% while the duration of the opportunity to run was first varied across values of 15, 45, and 90 s then subsequently across values of 5, 10, and 15 s. As run duration increased, postreinforcement pause duration in the presence of the wheel-running stimulus increased and local rates increased then decreased. In summary, inhibitory aftereffects of previous reinforcers occurred when both sucrose concentration and run duration varied; changes in responding were attributable to changes in the excitatory value of the stimuli signaling the two reinforcers.

Effects of selective breeding for increased wheel-running behavior on circadian timing of substrate oxidation and ingestive behavior

NARCIS (Netherlands)

Jonas, I.; Vaanholt, L. M.; Doornbos, M.; Garland, T.; Scheurink, A. J. W.; Nyakas, C.; van Dijk, G.; Garland Jr., T.

2010-01-01

Fluctuations in substrate preference and utilization across the circadian cycle may be influenced by the degree of physical activity and nutritional status. In the present study, we assessed these relationships in control mice and in mice from a line selectively bred for high voluntary wheel-running

Wheel-running reinforcement in free-feeding and food-deprived rats.

Science.gov (United States)

Belke, Terry W; Pierce, W David

2016-03-01

Rats experiencing sessions of 30min free access to wheel running were assigned to ad-lib and food-deprived groups, and given additional sessions of free wheel activity. Subsequently, both ad-lib and deprived rats lever pressed for 60s of wheel running on fixed ratio (FR) 1, variable ratio (VR) 3, VR 5, and VR 10 schedules, and on a response-initiated variable interval (VI) 30s schedule. Finally, the ad-lib rats were switched to food deprivation and the food-deprived rats were switched to free food, as rats continued responding on the response-initiated VI 30-s schedule. Wheel running functioned as reinforcement for both ad-lib and food-deprived rats. Food-deprived rats, however, ran faster and had higher overall lever-pressing rates than free-feeding rats. On the VR schedules, wheel-running rates positively correlated with local and overall lever pressing rates for deprived, but not ad-lib rats. On the response-initiated VI 30s schedule, wheel-running rates and lever-pressing rates changed for ad-lib rats switched to food deprivation, but not for food-deprived rats switched to free-feeding. The overall pattern of results suggested different sources of control for wheel running: intrinsic motivation, contingencies of automatic reinforcement, and food-restricted wheel running. An implication is that generalizations about operant responding for wheel running in food-deprived rats may not extend to wheel running and operant responding of free-feeding animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Running in a running wheel substitutes for stereotypies in mink (Mustela vison) but does it improve their welfare?

DEFF Research Database (Denmark)

Hansen, Steffen W; Damgaard, Birthe Marie

2009-01-01

This experiment investigated whether access to a running wheel affects the development of stereotypies during restricted feeding and whether selection for high or low levels of stereotypy affects the use of the running wheel. Sixty-two female mink kept in standard cages and selected for high or low...... levels of stereotypy were used. Thirty of these females had access to a running wheel whereas thirty-two female mink had no access to running wheels. The number of turns of the running wheel, behaviour, feed consumption, body weight and the concentration of plasma cortisol were measured during the winter...... period. Mink with access to a running wheel did not perform stereotypic behaviour and mink selected for a high level of stereotypies had more turns in the running wheel than mink selected for low levels of stereotypies. Mink with access to a running wheel used the running wheel for the same amount...

Blocking of conditioned taste avoidance induced by wheel running.

Science.gov (United States)

Pierce, W David; Heth, C Donald

2010-01-01

In Experiment 1, compared to non-reinforced presentation of a food stimulus (A-->no US), the association of a food stimulus with wheel running (A-->US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX-->US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX-->wheel training depended on the correlation between A-alone trials and wheel running-the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance. 2009 Elsevier B.V. All rights reserved.

Effect of short-term prefeeding and body weight on wheel running and responding reinforced by the opportunity to run in a wheel.

Science.gov (United States)

Belke, Terry W; Pierce, W David; Jensen, K

2004-07-30

A biobehavioural analysis of activity anorexia suggests that the motivation for physical activity is regulated by food supply and body weight. In the present experiment, food allocation was varied within subjects by prefeeding food-deprived rats 0, 5, 10 and 15 g of food before sessions of lever pressing for wheel-running reinforcement. The experiment assessed the effects of prefeeding on rates of wheel running, lever pressing, and postreinforcement pausing. Results showed that prefeeding animals 5 g of food had no effect. Prefeeding 10 g of food reduced lever pressing for wheel running and rates of wheel running without a significant change in body weight; the effect was, however, transitory. Prefeeding 15 g of food increased the animals' body weights, resulting in a sustained decrease of wheel running and lever pressing, and an increase in postreinforcement pausing. Overall the results indicate that the motivation for physical activity is regulated by changes in local food supply, but is sustained only when there is a concomitant change in body weight.

The Running Wheel Enhances Food Anticipatory Activity: An Exploratory Study.

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Flôres, Danilo E F L; Bettilyon, Crystal N; Jia, Lori; Yamazaki, Shin

2016-01-01

Rodents anticipate rewarding stimuli such as daily meals, mates, and stimulant drugs. When a single meal is provided daily at a fixed time of day, an increase in activity, known as food anticipatory activity (FAA), occurs several hours before feeding time. The factors affecting the expression of FAA have not been well-studied. Understanding these factors may provide clues to the undiscovered anatomical substrates of food entrainment. In this study we determined whether wheel-running activity, which is also rewarding to rodents, modulated the robustness of FAA. We found that access to a freely rotating wheel enhanced the robustness of FAA. This enhancement was lost when the wheel was removed. In addition, while prior exposure to a running wheel alone did not enhance FAA, the presence of a locked wheel did enhance FAA as long as mice had previously run in the wheel. Together, these data suggest that FAA, like wheel-running activity, is influenced by reward signaling.

Long-term oral feeding of lutein-fortified milk increases voluntary running distance in rats.

Directory of Open Access Journals (Sweden)

Megumi Matsumoto

Full Text Available To evaluate the effects of lutein-fortified milk administration on running exercise, a voluntary wheel-running model was performed in rats. Four-week-old F344 rats were administered test milk (10 mL/kg daily following a 4-h fasting period, and their running distances were measured each day for a 9-week period. Total weekly running distance significantly increased from the sixth week until the end of the test period in lutein-supplemented rats (lutein-fortified milk administered compared with control rats (vehicle administered. This increase was not apparent in rats administered lutein alone. In the lutein-fortified-milk exercise group compared with the sedentary control group, carnitine palitroyltransferase 1 (CPT-1, total AMP-activated protein kinase (tAMPK, and phosphorylated AMP-activated protein kinase (pAMPK contents were significantly increased in the gastrocnemius muscle, with a concomitant decrease in triglyceride and total cholesterol levels in the blood and liver. Furthermore, the lutein level in blood of lutein-administered rats significantly decreased with exercise. These results suggest that lutein-fortified milk may enhance the effect of exercise by effective utilization of lipids when combined with voluntary running.

Long-term oral feeding of lutein-fortified milk increases voluntary running distance in rats.

Science.gov (United States)

Matsumoto, Megumi; Hagio, Masahito; Inoue, Ryo; Mitani, Tomohiro; Yajima, Masako; Hara, Hiroshi; Yajima, Takaji

2014-01-01

To evaluate the effects of lutein-fortified milk administration on running exercise, a voluntary wheel-running model was performed in rats. Four-week-old F344 rats were administered test milk (10 mL/kg) daily following a 4-h fasting period, and their running distances were measured each day for a 9-week period. Total weekly running distance significantly increased from the sixth week until the end of the test period in lutein-supplemented rats (lutein-fortified milk administered) compared with control rats (vehicle administered). This increase was not apparent in rats administered lutein alone. In the lutein-fortified-milk exercise group compared with the sedentary control group, carnitine palitroyltransferase 1 (CPT-1), total AMP-activated protein kinase (tAMPK), and phosphorylated AMP-activated protein kinase (pAMPK) contents were significantly increased in the gastrocnemius muscle, with a concomitant decrease in triglyceride and total cholesterol levels in the blood and liver. Furthermore, the lutein level in blood of lutein-administered rats significantly decreased with exercise. These results suggest that lutein-fortified milk may enhance the effect of exercise by effective utilization of lipids when combined with voluntary running.

Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution

DEFF Research Database (Denmark)

Pedersen, Line; Idorn, Manja; Olofsson, Gitte H.

2016-01-01

Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models....... Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed...

Effect of sucrose availability and pre-running on the intrinsic value of wheel running as an operant and a reinforcing consequence.

Science.gov (United States)

Belke, Terry W; Pierce, W David

2014-03-01

The current study investigated the effect of motivational manipulations on operant wheel running for sucrose reinforcement and on wheel running as a behavioral consequence for lever pressing, within the same experimental context. Specifically, rats responded on a two-component multiple schedule of reinforcement in which lever pressing produced the opportunity to run in a wheel in one component of the schedule (reinforcer component) and wheel running produced the opportunity to consume sucrose solution in the other component (operant component). Motivational manipulations involved removal of sucrose contingent on wheel running and providing 1h of pre-session wheel running. Results showed that, in opposition to a response strengthening view, sucrose did not maintain operant wheel running. The motivational operations of withdrawing sucrose or providing pre-session wheel running, however, resulted in different wheel-running rates in the operant and reinforcer components of the multiple schedule; this rate discrepancy revealed the extrinsic reinforcing effects of sucrose on operant wheel running, but also indicated the intrinsic reinforcement value of wheel running across components. Differences in wheel-running rates between components were discussed in terms of arousal, undermining of intrinsic motivation, and behavioral contrast. Copyright © 2013 Elsevier B.V. All rights reserved.

Wheel running decreases palatable diet preference in Sprague-Dawley rats.

Science.gov (United States)

Moody, Laura; Liang, Joy; Choi, Pique P; Moran, Timothy H; Liang, Nu-Chu

2015-10-15

Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague-Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference. Published by Elsevier Inc.

Wheel running decreases palatable diet preference in Sprague-Dawley rats

Science.gov (United States)

Moody, Laura; Liang, Joy; Choi, Pique P.; Moran, Timothy H.; Liang, Nu-Chu

2015-01-01

Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel access initially showed complete avoidance of the two palatable diets, the avoidance of the HS diet was transient. Experiment 2 demonstrated that male rats developed decreased HF diet preferences regardless of the order of diet and wheel running access presentation. Running associated changes in HF diet preference in females, on the other hand, depended on the testing schedule. In female rats, simultaneous presentation of the HF diet and running access resulted in transient complete HF diet avoidance whereas running experience prior to HF diet access did not affect the high preference for the HF diet. Ovariectomy in females resulted in HF diet preference patterns that were similar to those in male rats during simultaneous exposure of HF and wheel running access but similar to intact females when running occurred before HF exposure. Overall, the results demonstrated wheel running associated changes in palatable diet preferences that were in part sex dependent. Furthermore, ovarian hormones play a role in some of the sex differences. These data reveal complexity in the mechanisms underlying exercise associated changes in palatable diet preference. PMID:25791204

Wheel running decreases palatable diet preference in Sprague-Dawley rats

OpenAIRE

Moody, Laura; Liang, Joy; Choi, Pique P.; Moran, Timothy H.; Liang, Nu-Chu

2015-01-01

Physical activity has beneficial effects on not only improving some disease conditions but also by preventing the development of multiple disorders. Experiments in this study examined the effects of wheel running on intakes of chow and palatable diet e.g. high fat (HF) or high sucrose (HS) diet in male and female Sprague Dawley rats. Experiment 1 demonstrated that acute wheel running results in robust HF or HS diet avoidance in male rats. Although female rats with running wheel...

Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease

Directory of Open Access Journals (Sweden)

Spires Tara L

2008-04-01

Full Text Available Abstract Background Huntington's disease (HD is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line, expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit. Results We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks, with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running. Conclusion These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment

Energy homeostasis and running wheel activity during pregnancy in the mouse.

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Ladyman, S R; Carter, K M; Grattan, D R

2018-05-05

Pregnancy and lactation are metabolically challenging states, where the mother must supply all the energy requirements for the developing fetus and growing pups respectively. The aim of the current study was to characterize many aspects of energy homeostasis before and during pregnancy in the mouse, and to examine the role of voluntary activity on changes in energy expenditure during pregnancy. In a secondary aim, we evaluate measures of energy homeostasis during pregnancy in mice that successfully reared their litter or in mice that went on to abandon their litter, to determine if an impairment in pregnancy-induced adaptation of energy homeostasis might underlie the abandonment of pups soon after birth. During pregnancy, food intake was increased, characterized by increased meal size and duration but not number of meals per day. The duration of time spent inactive, predicted to indicate sleep behaviour, was increased both early and late in pregnancy compared to pre-pregnancy levels. Increased x + y beam breaks, as a measure of activity increased during pregnancy and this reflected an increase in ambulatory behaviour in mid pregnancy and an increase in non-ambulatory movement in late pregnancy. Energy expenditure, as measured by indirect calorimetry, increased across pregnancy, likely due to the growth and development of fetal tissue. There was also a dramatic reduction in voluntary wheel running as soon as the mice became pregnant. Compared with successful pregnancies and lactations, pregnancies where pups were abandoned soon after birth were associated with reduced body weight gain and an increase in running wheel activity at the end of pregnancy, but no difference in food intake or energy expenditure. Overall, during pregnancy there are multiple adaptations to change energy homeostasis, resulting in partitioning of provisions of energy to the developing fetus and storing energy for future metabolic demands. Copyright © 2018 Elsevier Inc. All rights reserved.

Voluntary Exercise Prevents Cisplatin-Induced Muscle Wasting during Chemotherapy in Mice

DEFF Research Database (Denmark)

Hojman, Pernille; Fjelbye, Jonas; Zerahn, Bo

2014-01-01

, food intake as well as muscle mass, strength and signalling. Mice were treated weekly with 4 mg/kg cisplatin or saline for 6 weeks, and randomized to voluntary wheel running or not. Cisplatin treatment induced loss of body weight (29.8%, P ... as anorexia, impaired muscle strength (22.5% decrease, P wheel running during treatment attenuated body weight...... loss by 50% (P wheel running, nor was glucose tolerance improved. Exercise...

Naloxone attenuates the conditioned place preference induced by wheel running in rats.

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Lett, B T; Grant, V L; Koh, M T

2001-02-01

Pairings, during which an episode of wheel running is followed by confinement in a distinctive place, produce conditioned place preference (CPP) in rats. This finding indicates that wheel running has a rewarding effect that outlasts the activity itself. In two similar experiments, we tested the hypothesis that this rewarding effect of wheel running is mediated by endogenous opioids. During a paired trial, the rats in the naloxone group were first allowed to wheel run for 2 h, then injected with naloxone (0.5 or 0.1 mg/kg in Experiments 1 and 2, respectively), and 10 min later placed in a distinctive chamber. During an unpaired trial, these rats were confined in an adjoining chamber without wheel running. Naloxone was injected before placement in both chambers, so that if naloxone-induced conditioned place aversion occurred, it would have counteracting effects on performance during the preference test. The rats in the saline group were similarly treated, except that saline was injected instead of naloxone. CPP occurred in the saline group, but not in the naloxone group. Thus, naloxone attenuated the CPP induced by wheel running. This finding supports the hypothesis that the rewarding effect of wheel running is mediated by endogenous opioids.

Breast cancer pulmonary metastasis is increased in mice undertaking spontaneous physical training in the running wheel; a call for revising beneficial effects of exercise on cancer progression.

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Smeda, Marta; Przyborowski, Kamil; Proniewski, Bartosz; Zakrzewska, Agnieszka; Kaczor, Dawid; Stojak, Marta; Buczek, Elzbieta; Nieckarz, Zenon; Zoladz, Jerzy A; Wietrzyk, Joanna; Chlopicki, Stefan

2017-01-01

It has been repeatedly shown that regular aerobic exercise exerts beneficial effects on incidence and progression of cancer. However, the data regarding effects of exercise on metastatic dissemination remain conflicting. Therefore, in the present study the possible preventive effects of voluntary wheel running on primary tumor growth and metastases formation in the model of spontaneous pulmonary metastasis were analyzed after orthotopic injection of 4T1 breast cancer cells into mammary fat pads of female Balb/C mice. This study identified that in the mice injected with 4T1 breast cancer cells and running on the wheels (4T1 ex) the volume and size of the primary tumor were not affected, but the number of secondary nodules formed in the lungs was significantly increased compared to their sedentary counterparts (4T1 sed). This effect was associated with decreased NO production in the isolated aorta of exercising mice (4T1 ex), suggesting deterioration of endothelial function that was associated with lower platelet count without their overactivation. This was evidenced by comparable selectin P, active GPIIb/IIIa expression, fibrinogen and vWF binding on the platelet surface. In conclusion, voluntary wheel running appeared to impair, rather than improve endothelial function, and to promote, but not decrease metastasis in the murine orthotopic model of metastatic breast cancer. These results call for revising the notion of the persistent beneficial effects of voluntary exercise on breast cancer progression, though further studies are needed to elucidate mechanisms involved in pro-metastatic effects of voluntary exercise.

Reduction of extinction and reinstatement of cocaine seeking by wheel running in female rats.

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Zlebnik, Natalie E; Anker, Justin J; Gliddon, Luke A; Carroll, Marilyn E

2010-03-01

Previous work has shown that wheel running reduced the maintenance of cocaine self-administration in rats. In the present study, the effect of wheel running on extinction and reinstatement of cocaine seeking was examined. Female rats were trained to run in a wheel during 6-h sessions, and they were then catheterized and placed in an operant conditioning chamber where they did not have access to the wheel but were allowed to self-administer iv cocaine. Subsequently, rats were divided into four groups and were tested on the extinction and reinstatement of cocaine seeking while they had varying access to a wheel in an adjoining compartment. The four groups were assigned to the following wheel access conditions: (1) wheel running during extinction and reinstatement (WER), (2) wheel running during extinction and a locked wheel during reinstatement (WE), (3) locked wheel during extinction and wheel running during reinstatement (WR), and (4) locked wheel during extinction and reinstatement (WL). WE and WR were retested later to examine the effect of one session of wheel access on cocaine-primed reinstatement. There were no group differences in wheel revolutions, in rate of acquisition of cocaine self-administration, or in responding during maintenance when there was no wheel access. However, during extinction, WE and WER responded less than WR and WL. WR and WER had lower cocaine-primed reinstatement than WE and WL. One session of wheel exposure in WE also suppressed cocaine-primed reinstatement. Wheel running immediately and effectively reduced cocaine-seeking behavior, but concurrent access to running was necessary. Thus, exercise is a useful and self-sustaining intervention to reduce cocaine-seeking behavior.

Running behavior and its energy cost in mice selectively bred for high voluntary locomotor activity.

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Rezende, Enrico L; Gomes, Fernando R; Chappell, Mark A; Garland, Theodore

2009-01-01

Locomotion is central to behavior and intrinsic to many fitness-critical activities (e.g., migration, foraging), and it competes with other life-history components for energy. However, detailed analyses of how changes in locomotor activity and running behavior affect energy budgets are scarce. We quantified these effects in four replicate lines of house mice that have been selectively bred for high voluntary wheel running (S lines) and in their four nonselected control lines (C lines). We monitored wheel speeds and oxygen consumption for 24-48 h to determine daily energy expenditure (DEE), resting metabolic rate (RMR), locomotor costs, and running behavior (bout characteristics). Daily running distances increased roughly 50%-90% in S lines in response to selection. After we controlled for body mass effects, selection resulted in a 23% increase in DEE in males and a 6% increase in females. Total activity costs (DEE - RMR) accounted for 50%-60% of DEE in both S and C lines and were 29% higher in S males and 5% higher in S females compared with their C counterparts. Energetic costs of increased daily running distances differed between sexes because S females evolved higher running distances by running faster with little change in time spent running, while S males also spent 40% more time running than C males. This increase in time spent running impinged on high energy costs because the majority of running costs stemmed from "postural costs" (the difference between RMR and the zero-speed intercept of the speed vs. metabolic rate relationship). No statistical differences in these traits were detected between S and C females, suggesting that large changes in locomotor behavior do not necessarily effect overall energy budgets. Running behavior also differed between sexes: within S lines, males ran with more but shorter bouts than females. Our results indicate that selection effects on energy budgets can differ dramatically between sexes and that energetic constraints in S

Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons.

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Sobieraj, Jeffery C; Kim, Airee; Fannon, McKenzie J; Mandyam, Chitra D

2016-01-01

Exercise (physical activity) has been proposed as a treatment for drug addiction. In rodents, voluntary wheel running reduces cocaine and nicotine seeking during extinction, and reinstatement of cocaine seeking triggered by drug-cues. The purpose of this study was to examine the effects of chronic wheel running during withdrawal and protracted abstinence on extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats, and to determine a potential neurobiological correlate underlying the effects. Rats were given extended access to methamphetamine (0.05 mg/kg, 6 h/day) for 22 sessions. Rats were withdrawn and were given access to running wheels (wheel runners) or no wheels (sedentary) for 3 weeks after which they experienced extinction and reinstatement of methamphetamine seeking. Extended access to methamphetamine self-administration produced escalation in methamphetamine intake. Methamphetamine experience reduced running output, and conversely, access to wheel running during withdrawal reduced responding during extinction and, context- and cue-induced reinstatement of methamphetamine seeking. Immunohistochemical analysis of brain tissue demonstrated that wheel running during withdrawal did not regulate markers of methamphetamine neurotoxicity (neurogenesis, neuronal nitric oxide synthase, vesicular monoamine transporter-2) and cellular activation (c-Fos) in brain regions involved in relapse to drug seeking. However, reduced methamphetamine seeking was associated with running-induced reduction (and normalization) of the number of tyrosine hydroxylase immunoreactive neurons in the periaqueductal gray (PAG). The present study provides evidence that dopamine neurons of the PAG region show adaptive biochemical changes during methamphetamine seeking in methamphetamine dependent rats and wheel running abolishes these effects. Given that the PAG dopamine neurons project onto the structures of the extended amygdala, the present findings also

Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.

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Meek, Thomas H; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

2012-05-15

The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body

Wheel-running attenuates intravenous cocaine self-administration in rats: sex differences.

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Cosgrove, Kelly P; Hunter, Robb G; Carroll, Marilyn E

2002-10-01

This experiment examines the effect of access to a running-wheel on intravenous cocaine self-administration in male and female rats. Rats maintained at 85% of their free-feeding body weight were first exposed to the running-wheel alone during the 6-h sessions until behavior stabilized for 14 days. Intravenous cannulae were then implanted, and the rats were trained to self-administer a low dose of cocaine (0.2 mg/kg) under a fixed-ratio (FR 1) schedule during the 6-h sessions, while the wheel remained inactive and cocaine self-administration stabilized (cocaine-only condition). Next, the wheel access and cocaine self-administration were concurrently available followed by a period of cocaine-only. Behavior was allowed to stabilize for 10 days at each phase. During wheel access, cocaine infusions decreased by 21.9% in males and 70.6% in females compared to the cocaine-only condition; the effect was statistically significant in females. Infusions increased to baseline levels when wheel access was terminated. When cocaine infusions were concurrently available, wheel revolutions were reduced by 63.7% and 61.5% in males and females, respectively, compared to the wheel-only condition. This result did not differ due to sex, but it was statistically significant when data from males and females were combined. These results indicate that wheel-running activity had a greater suppressant effect on cocaine self-administration in females than in males, and in females, wheel-running and cocaine self-administration are substitutable as reinforcers.

Wheel-running in a transgenic mouse model of Alzheimer's disease: protection or symptom?

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Richter, Helene; Ambrée, Oliver; Lewejohann, Lars; Herring, Arne; Keyvani, Kathy; Paulus, Werner; Palme, Rupert; Touma, Chadi; Schäbitz, Wolf-Rüdiger; Sachser, Norbert

2008-06-26

Several studies on both humans and animals reveal benefits of physical exercise on brain function and health. A previous study on TgCRND8 mice, a transgenic model of Alzheimer's disease, reported beneficial effects of premorbid onset of long-term access to a running wheel on spatial learning and plaque deposition. Our study investigated the effects of access to a running wheel after the onset of Abeta pathology on behavioural, endocrinological, and neuropathological parameters. From day 80 of age, the time when Abeta deposition becomes apparent, TgCRND8 and wildtype mice were kept with or without running wheel. Home cage behaviour was analysed and cognitive abilities regarding object recognition memory and spatial learning in the Barnes maze were assessed. Our results show that, in comparison to Wt mice, Tg mice were characterised by impaired object recognition memory and spatial learning, increased glucocorticoid levels, hyperactivity in the home cage and high levels of stereotypic behaviour. Access to a running wheel had no effects on cognitive or neuropathological parameters, but reduced the amount of stereotypic behaviour in transgenics significantly. Furthermore, wheel-running was inversely correlated with stereotypic behaviour, suggesting that wheel-running may have stereotypic qualities. In addition, wheel-running positively correlated with plaque burden. Thus, in a phase when plaques are already present in the brain, it may be symptomatic of brain pathology, rather than protective. Whether or not access to a running wheel has beneficial effects on Alzheimer-like pathology and symptoms may therefore strongly depend on the exact time when the wheel is provided during development of the disease.

High levels of wheel running protect against behavioral sensitization to cocaine.

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Renteria Diaz, Laura; Siontas, Dora; Mendoza, Jose; Arvanitogiannis, Andreas

2013-01-15

Although there is no doubt that the direct action of stimulant drugs on the brain is necessary for sensitization to their behavioral stimulating effects, several experiments indicate that drug action is often not sufficient to produce sensitization. There is considerable evidence that many individual characteristics and experiential variables can modulate the behavioral and neural changes that are seen following repeated exposure to stimulant drugs. In the work presented here, we examined whether chronic wheel running would modulate behavioral sensitization to cocaine, and whether any such influence was contingent on individual differences in wheel running. We found that a 5- or 10-week experience with wheel running protects against behavioral sensitization to cocaine but only in animals with a natural tendency to run the most. Understanding the mechanism underlying the modulating effect of wheel running on behavioral sensitization may have important implications for future studies on the link between drug-induced behavioral and neural adaptations. Copyright © 2012 Elsevier B.V. All rights reserved.

Regional gray matter volume increases following 7days of voluntary wheel running exercise: a longitudinal VBM study in rats.

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Sumiyoshi, Akira; Taki, Yasuyuki; Nonaka, Hiroi; Takeuchi, Hikaru; Kawashima, Ryuta

2014-09-01

The effects of physical exercise on brain morphology in rodents have been well documented in histological studies. However, to further understand when and where morphological changes occur in the whole brain, a noninvasive neuroimaging method allowing an unbiased, comprehensive, and longitudinal investigation of brain morphology should be used. In this study, we investigated the effects of 7days of voluntary wheel running exercise on regional gray matter volume (rGMV) using longitudinal voxel-based morphometry (VBM) in rats. Eighteen pairs of adult male naïve Wistar rats were randomized to the exercise or control condition (one rat for each condition from each pair). Each rat was scanned in a 7.0-T MRI scanner at three time points: before exercise, after 7days of exercise, and after 7days of follow-up. The T2-weighted MRI images were segmented using the rat brain tissue priors that were recently published by our laboratory, and the intra- and inter-subject template creation steps were followed. Longitudinal VBM analysis revealed significant increases in rGMV in the motor, somatosensory, association, and visual cortices in the exercise group. Among these brain regions, rGMV changes in the motor cortex were positively correlated with the total distance that was run during the 7days of exercise. In addition, the effects of 7days of exercise on rGMV persisted after 7days of follow-up. These results support the utility of a longitudinal VBM study in rats and provide new insights into experience-dependent structural brain plasticity in naïve adult animals. Copyright © 2014 Elsevier Inc. All rights reserved.

Nocturnal to Diurnal Switches with Spontaneous Suppression of Wheel-Running Behavior in a Subterranean Rodent.

Directory of Open Access Journals (Sweden)

Patricia Tachinardi

Full Text Available Several rodent species that are diurnal in the field become nocturnal in the lab. It has been suggested that the use of running-wheels in the lab might contribute to this timing switch. This proposition is based on studies that indicate feed-back of vigorous wheel-running on the period and phase of circadian clocks that time daily activity rhythms. Tuco-tucos (Ctenomys aff. knighti are subterranean rodents that are diurnal in the field but are robustly nocturnal in laboratory, with or without access to running wheels. We assessed their energy metabolism by continuously and simultaneously monitoring rates of oxygen consumption, body temperature, general motor and wheel running activity for several days in the presence and absence of wheels. Surprisingly, some individuals spontaneously suppressed running-wheel activity and switched to diurnality in the respirometry chamber, whereas the remaining animals continued to be nocturnal even after wheel removal. This is the first report of timing switches that occur with spontaneous wheel-running suppression and which are not replicated by removal of the wheel.

Nocturnal to Diurnal Switches with Spontaneous Suppression of Wheel-Running Behavior in a Subterranean Rodent

Science.gov (United States)

Tachinardi, Patricia; Tøien, Øivind; Valentinuzzi, Veronica S.; Buck, C. Loren; Oda, Gisele A.

2015-01-01

Several rodent species that are diurnal in the field become nocturnal in the lab. It has been suggested that the use of running-wheels in the lab might contribute to this timing switch. This proposition is based on studies that indicate feed-back of vigorous wheel-running on the period and phase of circadian clocks that time daily activity rhythms. Tuco-tucos (Ctenomys aff. knighti) are subterranean rodents that are diurnal in the field but are robustly nocturnal in laboratory, with or without access to running wheels. We assessed their energy metabolism by continuously and simultaneously monitoring rates of oxygen consumption, body temperature, general motor and wheel running activity for several days in the presence and absence of wheels. Surprisingly, some individuals spontaneously suppressed running-wheel activity and switched to diurnality in the respirometry chamber, whereas the remaining animals continued to be nocturnal even after wheel removal. This is the first report of timing switches that occur with spontaneous wheel-running suppression and which are not replicated by removal of the wheel. PMID:26460828

Reinforcement of wheel running in BALB/c mice: role of motor activity and endogenous opioids.

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Vargas-Pérez, Héctor; Sellings, Laurie H L; Paredes, Raúl G; Prado-Alcalá, Roberto A; Díaz, José-Luis

2008-11-01

The authors investigated the effect of the opioid antagonist naloxone on wheel-running behavior in Balb/c mice. Naloxone delayed the acquisition of wheel-running behavior, but did not reduce the expression of this behavior once acquired. Delayed acquisition was not likely a result of reduced locomotor activity, as naloxone-treated mice did not exhibit reduced wheel running after the behavior was acquired, and they performed normally on the rotarod test. However, naloxone-blocked conditioned place preference for a novel compartment paired previously with wheel running, suggesting that naloxone may delay wheel-running acquisition by blocking the rewarding or reinforcing effects of the behavior. These results suggest that the endogenous opioid system mediates the initial reinforcing effects of wheel running that are important in acquisition of the behavior.

Effects of genetic background and environmental novelty on wheel running as a rewarding behaviour in mice.

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de Visser, Leonie; van den Bos, Ruud; Stoker, Astrid K; Kas, Martien J H; Spruijt, Berry M

2007-02-27

Recent studies suggest running wheel activity to be naturally rewarding and reinforcing; considering the shared neuro-behavioural characteristics with drug-induced reward situations, wheel running behaviour gains interest as a tool to study mechanisms underlying reward-sensitivity. Previously, we showed that wheel running has the potential to disrupt the daily organization of home cage behaviour in female C57BL/6 [de Visser L, van den Bos R, Spruijt BM. Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion. Behav Brain Res 2005;160:382-8]. In the present study, we investigated the effects of novelty-induced stress on wheel running and its impact on home cage behaviour in male C57BL/6 and DBA/2 mice. Our aim was to determine whether wheel running may be used as a tool to study both genetic and environmentally induced differences in sensitivity to rewarding behaviour in mice. One group of male mice was placed in an automated home cage observation system for 2 weeks with a wheel integrated in the cage. A second group of mice was allowed to habituate to this cage for 1 week before a running wheel was introduced. Results showed a pronounced sensitising effect of novelty on the level of wheel running in C57Bl/6 mice but not in DBA mice. Overall levels of wheel running were higher in DBA/2 mice. Furthermore, wheel running affected circadian rhythmicity in DBA/2 mice but not in C57BL/6 mice. From these findings we tentatively suggest that wheel running behaviour could serve as a tool to study the interaction between genetic and environmental factors in sensitivity to rewarding behaviour in mice. As it is displayed spontaneously and easy to monitor, wheel running may be well suitable to be included in high-throughput phenotyping assays.

Body weight manipulation, reinforcement value and choice between sucrose and wheel running: a behavioral economic analysis.

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Belke, Terry W; Pierce, W David

2009-02-01

Twelve female Long-Evans rats were exposed to concurrent variable (VR) ratio schedules of sucrose and wheel-running reinforcement (Sucrose VR 10 Wheel VR 10; Sucrose VR 5 Wheel VR 20; Sucrose VR 20 Wheel VR 5) with predetermined budgets (number of responses). The allocation of lever pressing to the sucrose and wheel-running alternatives was assessed at high and low body weights. Results showed that wheel-running rate and lever-pressing rates for sucrose and wheel running increased, but the choice of wheel running decreased at the low body weight. A regression analysis of relative consumption as a function of relative price showed that consumption shifted toward sucrose and interacted with price differences in a manner consistent with increased substitutability. Demand curves showed that demand for sucrose became less elastic while demand for wheel running became more elastic at the low body weight. These findings reflect an increase in the difference in relative value of sucrose and wheel running as body weight decreased. Discussion focuses on the limitations of response rates as measures of reinforcement value. In addition, we address the commonalities between matching and demand curve equations for the analysis of changes in relative reinforcement value.

Dissociation of conditioned taste avoidance from conditioned disgust reactions induced by wheel running in rats.

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Grant, Virginia L; McDonald, Sarah V; Sheppard, Robyn C; Caldwell, Catherine L; Heeley, Thomas H; Brown, Adam R; Martin, Gerard M

2012-06-01

It is well established that wheel running in rats produces conditioned taste avoidance; that is, rats that run in wheels after consuming a novel-tasting solution later consume less of that solution than rats that do not run. In experiment 1, we found that wheel running also produces conditioned disgust reactions, indicated by gapes elicited by both the taste and context that were experienced before running. Experiment 2 showed that the conditioned disgust reactions were likely not due to running itself but to a by-product of running, the rocking of the wheel that occurs when the running stops. When rocking was reduced, the disgust reactions were also reduced, but consumption of the taste solution was not changed, showing dissociation of conditioned taste avoidance and disgust. These findings indicate that the taste avoidance induced by wheel running itself is more like the taste avoidance produced by rewarding drugs than that produced by nausea-inducing drugs. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Improved infrared-sensing running wheel systems with an effective exercise activity indicator.

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Chen, Chi-Chun; Chang, Ming-Wen; Chang, Ching-Ping; Chang, Wen-Ying; Chang, Shin-Chieh; Lin, Mao-Tsun; Yang, Chin-Lung

2015-01-01

This paper describes an infrared-sensing running wheel (ISRW) system for the quantitative measurement of effective exercise activity in rats. The ISRW system provides superior exercise training compared with commercially available traditional animal running platforms. Four infrared (IR) light-emitting diode/detector pairs embedded around the rim of the wheel detect the rat's real-time position; the acrylic wheel has a diameter of 55 cm and a thickness of 15 cm, that is, it is larger and thicker than traditional exercise wheels, and it is equipped with a rubber track. The acrylic wheel hangs virtually frictionless, and a DC motor with an axially mounted rubber wheel, which has a diameter of 10 cm, drives the acrylic wheel from the outer edge. The system can automatically train rats to run persistently. The proposed system can determine effective exercise activity (EEA), with the IR sensors (which are connected to a conventional PC) recording the rat exercise behavior. A prototype of the system was verified by a hospital research group performing ischemic stroke experiments on rats by considering middle cerebral artery occlusion. The experimental data demonstrated that the proposed system provides greater neuroprotection in an animal stroke model compared with a conventional treadmill and a motorized running wheel for a given exercise intensity. The quantitative exercise effectiveness indicator showed a 92% correlation between an increase in the EEA and a decrease in the infarct volume. This indicator can be used as a noninvasive and objective reference in clinical animal exercise experiments.

Improved infrared-sensing running wheel systems with an effective exercise activity indicator.

Directory of Open Access Journals (Sweden)

Chi-Chun Chen

Full Text Available This paper describes an infrared-sensing running wheel (ISRW system for the quantitative measurement of effective exercise activity in rats. The ISRW system provides superior exercise training compared with commercially available traditional animal running platforms. Four infrared (IR light-emitting diode/detector pairs embedded around the rim of the wheel detect the rat's real-time position; the acrylic wheel has a diameter of 55 cm and a thickness of 15 cm, that is, it is larger and thicker than traditional exercise wheels, and it is equipped with a rubber track. The acrylic wheel hangs virtually frictionless, and a DC motor with an axially mounted rubber wheel, which has a diameter of 10 cm, drives the acrylic wheel from the outer edge. The system can automatically train rats to run persistently. The proposed system can determine effective exercise activity (EEA, with the IR sensors (which are connected to a conventional PC recording the rat exercise behavior. A prototype of the system was verified by a hospital research group performing ischemic stroke experiments on rats by considering middle cerebral artery occlusion. The experimental data demonstrated that the proposed system provides greater neuroprotection in an animal stroke model compared with a conventional treadmill and a motorized running wheel for a given exercise intensity. The quantitative exercise effectiveness indicator showed a 92% correlation between an increase in the EEA and a decrease in the infarct volume. This indicator can be used as a noninvasive and objective reference in clinical animal exercise experiments.

Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

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Liang, Nu-Chu; Bello, Nicholas T.; Moran, Timothy H.

2015-01-01

The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) µ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain. PMID:25668514

Taste avoidance induced by wheel running: effects of backward pairings and robustness of conditioned taste aversion.

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Salvy, Sarah-Jeanne; Pierce, W David; Heth, Donald C; Russell, James C

2004-09-15

Rats repeatedly exposed to a distinctive novel solution (conditioned stimulus, CS) followed by the opportunity to run in a wheel subsequently drink less of this solution. Investigations on this phenomenon indicate that wheel running is an effective unconditioned stimulus (US) for establishing conditioned taste aversion (CTA) when using a forward conditioning procedure (i.e., the US-wheel running follows the CS-taste). However, other studies show that wheel running produces reliable preference for a distinctive place when pairings are backward (i.e., the CS-location follows the US-wheel running). One possibility to account for these results is that rewarding aftereffects of wheel running conditioned preference to the CS. The main objective of the present study was to assess the effects of backward conditioning using wheel running as the US and a distinctive taste as the CS. In a between-groups design, two experimental groups [i.e., forward (FC) and backward conditioning (BC)] and two control groups [CS-taste alone (TA) and CS-US unpaired (UNP)] were compared. Results from this experiment indicated that there is less suppression of drinking when a CS-taste followed a bout of wheel running. In fact, rats in the BC group drank more of the paired solution than all the other groups.

A novel mouse running wheel that senses individual limb forces: biomechanical validation and in vivo testing

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Roach, Grahm C.; Edke, Mangesh

2012-01-01

Biomechanical data provide fundamental information about changes in musculoskeletal function during development, adaptation, and disease. To facilitate the study of mouse locomotor biomechanics, we modified a standard mouse running wheel to include a force-sensitive rung capable of measuring the normal and tangential forces applied by individual paws. Force data were collected throughout the night using an automated threshold trigger algorithm that synchronized force data with wheel-angle data and a high-speed infrared video file. During the first night of wheel running, mice reached consistent running speeds within the first 40 force events, indicating a rapid habituation to wheel running, given that mice generated >2,000 force-event files/night. Average running speeds and peak normal and tangential forces were consistent throughout the first four nights of running, indicating that one night of running is sufficient to characterize the locomotor biomechanics of healthy mice. Twelve weeks of wheel running significantly increased spontaneous wheel-running speeds (16 vs. 37 m/min), lowered duty factors (ratio of foot-ground contact time to stride time; 0.71 vs. 0.58), and raised hindlimb peak normal forces (93 vs. 115% body wt) compared with inexperienced mice. Peak normal hindlimb-force magnitudes were the primary force component, which were nearly tenfold greater than peak tangential forces. Peak normal hindlimb forces exceed the vertical forces generated during overground running (50-60% body wt), suggesting that wheel running shifts weight support toward the hindlimbs. This force-instrumented running-wheel system provides a comprehensive, noninvasive screening method for monitoring gait biomechanics in mice during spontaneous locomotion. PMID:22723628

Cocaine-induced locomotor activity in rats selectively bred for low and high voluntary running behavior.

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Brown, Jacob D; Green, Caroline L; Arthur, Ian M; Booth, Frank W; Miller, Dennis K

2015-02-01

The rewarding effects of physical activity and abused drugs are caused by stimulation of similar brain pathways. Low (LVR) and high (HVR) voluntary running lines were developed by selectively breeding Wistar rats on running distance performance on postnatal days 28-34. We hypothesized that LVR rats would be more sensitive to the locomotor-activating effects of cocaine than HVR rats due to their lower motivation for wheel running. We investigated how selection for LVR or HVR behavior affects inherited activity responses: (a) open field activity levels, (b) habituation to an open field environment, and (c) the locomotor response to cocaine. Open field activity was measured for 80 min on three successive days (days 1-3). Data from the first 20 min were analyzed to determine novelty-induced locomotor activity (day 1) and the habituation to the environment (days 1-3). On day 3, rats were acclimated to the chamber for 20 min and then received saline or cocaine (10, 20, or 30 mg/kg) injection. Dopamine transporter (DAT) protein in the nucleus accumbens was measured via Western blot. Selecting for low and high voluntary running behavior co-selects for differences in inherent (HVR > LVR) and cocaine-induced (LVR > HVR) locomotor activity levels. The differences in the selected behavioral measures do not appear to correlate with DAT protein levels. LVR and HVR rats are an intriguing physical activity model for studying the interactions between genes related to the motivation to run, to use drugs of abuse, and to exhibit locomotor activity.

Effect of Light/Dark Cycle on Wheel Running and Responding Reinforced by the Opportunity to Run Depends on Postsession Feeding Time

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Belke, T. W.; Mondona, A. R.; Conrad, K. M.; Poirier, K. F.; Pickering, K. L.

2008-01-01

Do rats run and respond at a higher rate to run during the dark phase when they are typically more active? To answer this question, Long Evans rats were exposed to a response-initiated variable interval 30-s schedule of wheel-running reinforcement during light and dark cycles. Wheel-running and local lever-pressing rates increased modestly during…

Wheel-running activity and energy metabolism in relation to ambient temperature in mice selected for high wheel-running activity

NARCIS (Netherlands)

Vaanholt, Lobke M.; Garland, Theodore; Daan, Serge; Visser, G. Henk; Garland Jr., Theodore; Heldmaier, G.

Interrelationships between ambient temperature, activity, and energy metabolism were explored in mice that had been selectively bred for high spontaneous wheel-running activity and their random-bred controls. Animals were exposed to three different ambient temperatures (10, 20 and 30 degrees C) and

A Brief Opportunity to Run Does Not Function as a Reinforcer for Mice Selected for High Daily Wheel-Running Rates

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Belke, Terry W.; Garland, Theodore, Jr.

2007-01-01

Mice from replicate lines, selectively bred based on high daily wheel-running rates, run more total revolutions and at higher average speeds than do mice from nonselected control lines. Based on this difference it was assumed that selected mice would find the opportunity to run in a wheel a more efficacious consequence. To assess this assumption…

Effects of early-life exposure to Western diet and wheel access on metabolic syndrome profiles in mice bred for high voluntary exercise.

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Meek, T H; Eisenmann, J C; Keeney, B K; Hannon, R M; Dlugosz, E M; Garland, T

2014-03-01

Experimental studies manipulating diet and exercise have shown varying effects on metabolic syndrome components in both humans and rodents. To examine the potential interactive effects of diet, exercise and genetic background, we studied mice from four replicate lines bred (52 generations) for high voluntary wheel running (HR lines) and four unselected control lines (C). At weaning, animals were housed for 60 days with or without wheels and fed either a standard chow or Western diet (WD, 42% kcal from fat). Four serial (three juvenile and one adult) blood samples were taken to measure fasting total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides and glucose. Western diet was obesogenic for all mice, even after accounting for the amount of wheel running and kilojoules consumed. Western diet significantly raised glucose as well as TC and HDL-C concentrations. At the level of individual variation (repeatability), there was a modest correlation (r = 0.3-0.5) of blood lipids over time, which was reduced with wheel access and/or WD. Neither genetic selection history nor wheel access had a statistically significant effect on blood lipids. However, HR and C mice had divergent ontogenetic trajectories for body mass and caloric intake. HR mice also had lower adiposity, an effect that was dependent on wheel access. The environmental factors of diet and wheel access had pronounced effects on body mass, food consumption and fasting glucose concentrations, interacting with each other and/or with genetic strain. These data underscore the importance (and often unpredictable nature) of genotype-by-environment and environment-by-environment interactions when studying body weight regulation. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Responding for sucrose and wheel-running reinforcement: effect of D-amphetamine.

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Belke, T W; Oldford, A C; Forgie, M Y; Beye, J A

2005-07-01

The present study assessed the effect of D-amphetamine on responding maintained by wheel-running and sucrose reinforcement. Six male albino Wistar rats were placed in running wheels and exposed to a fixed-interval 30-s schedule that produced either a drop of 5% sucrose solution or the opportunity to run for 15 s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. Doses of 0.25, 0.5, 1.0, 1.5, and 3.0 mg/kg D-amphetamine were administered by i.p. injection 20 min prior to a session. As the dose increased, index of curvature values decreased toward zero and rate-dependency plots revealed increases in lower rates early in the interval and decreases in higher rates toward the end of the interval. Effects were similar in the presence of both stimuli. However, an analysis of post-reinforcement pauses and local response rates broken down by transitions revealed a differential effect. As the dose increased, local response rates following a wheel-running reinforcer were affected more than those following a sucrose reinforcer.

A novel instrumented multipeg running wheel system, Step-Wheel, for monitoring and controlling complex sequential stepping in mice.

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Kitsukawa, Takashi; Nagata, Masatoshi; Yanagihara, Dai; Tomioka, Ryohei; Utsumi, Hideko; Kubota, Yasuo; Yagi, Takeshi; Graybiel, Ann M; Yamamori, Tetsuo

2011-07-01

Motor control is critical in daily life as well as in artistic and athletic performance and thus is the subject of intense interest in neuroscience. Mouse models of movement disorders have proven valuable for many aspects of investigation, but adequate methods for analyzing complex motor control in mouse models have not been fully established. Here, we report the development of a novel running-wheel system that can be used to evoke simple and complex stepping patterns in mice. The stepping patterns are controlled by spatially organized pegs, which serve as footholds that can be arranged in adjustable, ladder-like configurations. The mice run as they drink water from a spout, providing reward, while the wheel turns at a constant speed. The stepping patterns of the mice can thus be controlled not only spatially, but also temporally. A voltage sensor to detect paw touches is attached to each peg, allowing precise registration of footfalls. We show that this device can be used to analyze patterns of complex motor coordination in mice. We further demonstrate that it is possible to measure patterns of neural activity with chronically implanted tetrodes as the mice engage in vigorous running bouts. We suggest that this instrumented multipeg running wheel (which we name the Step-Wheel System) can serve as an important tool in analyzing motor control and motor learning in mice.

Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

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Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

2016-08-01

We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. Copyright © 2016 the American Physiological Society.

Plasma adiponectin is increased in mice selectively bred for high wheel-running activity, but not by wheel running per se

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Vaanholt, L. M.; Meerlo, P.; Garland, T.; Visser, G. H.; van Dijk, G.

2007-01-01

Mice selectively bred for high wheel-running activity (S) have decreased fat content compared to mice from randomly bred control (C) lines. We explored whether this difference was associated with alterations in levels of circulating hormones involved in regulation of food intake and energy balance,

The reinforcing property and the rewarding aftereffect of wheel running in rats: a combination of two paradigms.

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Belke, Terry W; Wagner, Jason P

2005-02-28

Wheel running reinforces the behavior that generates it and produces a preference for the context that follows it. The goal of the present study was to demonstrate both of these effects in the same animals. Twelve male Wistar rats were first exposed to a fixed-interval 30 s schedule of wheel-running reinforcement. The operant was lever-pressing and the reinforcer was the opportunity to run for 45 s. Following this phase, the method of place conditioning was used to test for a rewarding aftereffect following operant sessions. On alternating days, half the rats responded for wheel-running reinforcement while the other half remained in their home cage. Upon completion of the wheel-running reinforcement sessions, rats that ran and rats that remained in their home cages were placed into a chamber of a conditioned place preference (CPP) apparatus for 30 min. Each animal received six pairings of a distinctive context with wheel running and six pairings of a different context with their home cage. On the test day, animals were free to move between the chambers for 10 min. Results showed a conditioned place preference for the context associated with wheel running; however, time spent in the context associated with running was not related to wheel-running rate, lever-pressing rate, or post-reinforcement pause duration. (c) 2004 Elsevier B.V. All rights reserved.

Reinforcement Value and Substitutability of Sucrose and Wheel Running: Implications for Activity Anorexia

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Belke, Terry W.; Duncan, Ian D.; Pierce, W. David

2006-01-01

Choice between sucrose and wheel-running reinforcement was assessed in two experiments. In the first experiment, ten male Wistar rats were exposed to concurrent VI 30 s VI 30 s schedules of wheel-running and sucrose reinforcement. Sucrose concentration varied across concentrations of 2.5, 7.5, and 12.5%. As concentration increased, more behavior…

An Innovative Running Wheel-based Mechanism for Improved Rat Training Performance.

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Chen, Chi-Chun; Yang, Chin-Lung; Chang, Ching-Ping

2016-09-19

This study presents an animal mobility system, equipped with a positioning running wheel (PRW), as a way to quantify the efficacy of an exercise activity for reducing the severity of the effects of the stroke in rats. This system provides more effective animal exercise training than commercially available systems such as treadmills and motorized running wheels (MRWs). In contrast to an MRW that can only achieve speeds below 20 m/min, rats are permitted to run at a stable speed of 30 m/min on a more spacious and high-density rubber running track supported by a 15 cm wide acrylic wheel with a diameter of 55 cm in this work. Using a predefined adaptive acceleration curve, the system not only reduces the operator error but also trains the rats to run persistently until a specified intensity is reached. As a way to evaluate the exercise effectiveness, real-time position of a rat is detected by four pairs of infrared sensors deployed on the running wheel. Once an adaptive acceleration curve is initiated using a microcontroller, the data obtained by the infrared sensors are automatically recorded and analyzed in a computer. For comparison purposes, 3 week training is conducted on rats using a treadmill, an MRW and a PRW. After surgically inducing middle cerebral artery occlusion (MCAo), modified neurological severity scores (mNSS) and an inclined plane test were conducted to assess the neurological damages to the rats. PRW is experimentally validated as the most effective among such animal mobility systems. Furthermore, an exercise effectiveness measure, based on rat position analysis, showed that there is a high negative correlation between the effective exercise and the infarct volume, and can be employed to quantify a rat training in any type of brain damage reduction experiments.

The use of a running wheel to measure activity in rodents: relationship to energy balance, general activity, and reward.

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Novak, Colleen M; Burghardt, Paul R; Levine, James A

2012-03-01

Running wheels are commonly employed to measure rodent physical activity in a variety of contexts, including studies of energy balance and obesity. There is no consensus on the nature of wheel-running activity or its underlying causes, however. Here, we will begin by systematically reviewing how running wheel availability affects physical activity and other aspects of energy balance in laboratory rodents. While wheel running and physical activity in the absence of a wheel commonly correlate in a general sense, in many specific aspects the two do not correspond. In fact, the presence of running wheels alters several aspects of energy balance, including body weight and composition, food intake, and energy expenditure of activity. We contend that wheel-running activity should be considered a behavior in and of itself, reflecting several underlying behavioral processes in addition to a rodent's general, spontaneous activity. These behavioral processes include defensive behavior, predatory aggression, and depression- and anxiety-like behaviors. As it relates to energy balance, wheel running engages several brain systems-including those related to the stress response, mood, and reward, and those responsive to growth factors-that influence energy balance indirectly. We contend that wheel-running behavior represents factors in addition to rodents' tendency to be physically active, engaging additional neural and physiological mechanisms which can then independently alter energy balance and behavior. Given the impact of wheel-running behavior on numerous overlapping systems that influence behavior and physiology, this review outlines the need for careful design and interpretation of studies that utilize running wheels as a means for exercise or as a measurement of general physical activity. Copyright © 2012 Elsevier Ltd. All rights reserved.

The use of a running wheel to measure activity in rodents: Relationship to energy balance, general activity, and reward

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Levine, James A.

2015-01-01

Running wheels are commonly employed to measure rodent physical activity in a variety of contexts, including studies of energy balance and obesity. There is no consensus on the nature of wheel-running activity or its underlying causes, however. Here, we will begin by systematically reviewing how running wheel availability affects physical activity and other aspects of energy balance in laboratory rodents. While wheel running and physical activity in the absence of a wheel commonly correlate in a general sense, in many specific aspects the two do not correspond. In fact, the presence of running wheels alters several aspects of energy balance, including body weight and composition, food intake, and energy expenditure of activity. We contend that wheel-running activity should be considered a behavior in and of itself, reflecting several underlying behavioral processes in addition to a rodent's general, spontaneous activity. These behavioral processes include defensive behavior, predatory aggression, and depression- and anxiety-like behaviors. As it relates to energy balance, wheel running engages several brain systems—including those related to the stress response, mood, and reward, and those responsive to growth factors—that influence energy balance indirectly. We contend that wheel-running behavior represents factors in addition to rodents' tendency to be physically active, engaging additional neural and physiological mechanisms which can then independently alter energy balance and behavior. Given the impact of wheel-running behavior on numerous overlapping systems that influence behavior and physiology, this review outlines the need for careful design and interpretation of studies that utilize running wheels as a means for exercise or as a measurement of general physical activity. PMID:22230703

Depression of home cage wheel running: a reliable and clinically relevant method to assess migraine pain in rats.

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Kandasamy, Ram; Lee, Andrea T; Morgan, Michael M

2017-12-01

The development of new anti-migraine treatments is limited by the difficulty inassessing migraine pain in laboratory animals. Depression of activity is one of the few diagnostic criteria formigraine that can be mimicked in rats. The goal of the present study was to test the hypothesis thatdepression of home cage wheel running is a reliable and clinically relevant method to assess migraine painin rats. Adult female rats were implanted with a cannula to inject allyl isothiocyanate (AITC) onto the dura to induce migraine pain, as has been shown before. Rats recovered from implantation surgery for 8 days in cages containing a running wheel. Home cage wheel running was recorded 23 h a day. AITC and the migraine medication sumatriptan were administered in the hour prior to onset of the dark phase. Administration of AITC caused a concentration-dependent decrease in wheel running that lasted 3 h. The duration and magnitude of AITC-induced depression of wheel running was consistent following three repeated injections spaced 48 h apart. Administration of sumatriptan attenuated AITC-induced depressionof wheel running when a large dose (1 mg/kg) was administered immediately following AITC administration. Wheel running patterns did not change when sumatriptan was given to naïve rats. These data indicate that home cage wheel running is a sensitive, reliable, and clinically relevant method to assess migraine pain in the rat.

Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion.

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de Visser, Leonie; van den Bos, Ruud; Spruijt, Berry M

2005-05-28

This paper introduces automated observations in a modular home cage system as a tool to measure the effects of wheel running on the time distribution and daily organization of cage floor locomotor activity in female C57BL/6 mice. Mice (n = 16) were placed in the home cage system for 6 consecutive days. Fifty percent of the subjects had free access to a running wheel that was integrated in the home cage. Overall activity levels in terms of duration of movement were increased by wheel running, while time spent inside a sheltering box was decreased. Wheel running affected the hourly pattern of movement during the animals' active period of the day. Mice without a running wheel, in contrast to mice with a running wheel, showed a clear differentiation between novelty-induced and baseline levels of locomotion as reflected by a decrease after the first day of introduction to the home cage. The results are discussed in the light of the use of running wheels as a tool to measure general activity and as an object for environmental enrichment. Furthermore, the possibilities of using automated home cage observations for e.g. behavioural phenotyping are discussed.

Effects of voluntary running exercise on bone histology in type 2 diabetic rats.

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Yuri Takamine

Full Text Available The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21 rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18 rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11, OLETF exercise group (O-Ex; n = 10, LETO sedentary group (L-Sed; n = 9, and LETO exercise group (L-Ex; n = 9. All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5-25 weeks of age. In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.

Effects of voluntary running exercise on bone histology in type 2 diabetic rats.

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Takamine, Yuri; Ichinoseki-Sekine, Noriko; Tsuzuki, Takamasa; Yoshihara, Toshinori; Naito, Hisashi

2018-01-01

The incidence of obesity in children and adolescents, which may lead to type 2 diabetes, is increasing. Exercise is recommended to prevent and improve diabetes. However, little is known about the bone marrow environment at the onset of diabetes in the young, and it is unclear whether exercise training is useful for maintaining bone homeostasis, such as mechanical and histological properties. Thus, this study clarified the histological properties of bone and whether exercise contributes to maintaining bone homeostasis at the onset of type 2 diabetes in rats. Four-week-old male Otsuka Long-Evans Tokushima Fatty (OLETF; n = 21) rats as a diabetic model and Long-Evans Tokushima Otsuka (LETO; n = 18) rats as a control were assigned randomly to four groups: the OLETF sedentary group (O-Sed; n = 11), OLETF exercise group (O-Ex; n = 10), LETO sedentary group (L-Sed; n = 9), and LETO exercise group (L-Ex; n = 9). All rats in the exercise group were allowed free access to a steel running wheel for 20 weeks (5-25 weeks of age). In the glucose tolerance test, blood glucose level was higher in the O-Sed group than that in the L-Sed and L-Ex groups, and was markedly suppressed by the voluntary running exercise of O-Ex rats. The energy to fracture and the two-dimensional bone volume at 25 weeks of age did not differ significantly among the groups, though the maximum breaking force and stiffness were lower in OLETF rats. However, bone marrow fat volume was greater in O-Sed than that in L-Sed and L-Ex rats, and was markedly suppressed by wheel running in the O-Ex rats. Our results indicate that exercise has beneficial effects not only for preventing diabetes but also on normal bone remodeling at an early age.

Selective Breeding and Short-Term Access to a Running Wheel Alter Stride Characteristics in House Mice.

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Claghorn, Gerald C; Thompson, Zoe; Kay, Jarren C; Ordonez, Genesis; Hampton, Thomas G; Garland, Theodore

Postural and kinematic aspects of running may have evolved to support high runner (HR) mice to run approximately threefold farther than control mice. Mice from four replicate HR lines selectively bred for high levels of voluntary wheel running show many differences in locomotor behavior and morphology as compared with four nonselected control (C) lines. We hypothesized that HR mice would show stride alterations that have coadapted with locomotor behavior, morphology, and physiology. More specifically, we predicted that HR mice would have stride characteristics that differed from those of C mice in ways that parallel some of the adaptations seen in highly cursorial animals. For example, we predicted that limbs of HR mice would swing closer to the parasagittal plane, resulting in a two-dimensional measurement of narrowed stance width. We also expected that some differences between HR and C mice might be amplified by 6 d of wheel access, as is used to select breeders each generation. We used the DigiGait Imaging System (Mouse Specifics) to capture high-speed videos in ventral view as mice ran on a motorized treadmill across a range of speeds and then to automatically calculate several aspects of strides. Young adults of both sexes were tested both before and after 6 d of wheel access. Stride length, stride frequency, stance width, stance time, brake time, propel time, swing time, duty factor, and paw contact area were analyzed using a nested analysis of covariance, with body mass as a covariate. As expected, body mass and treadmill speed affected nearly every analyzed metric. Six days of wheel access also affected nearly every measure, indicating pervasive training effects, in both HR and C mice. As predicted, stance width was significantly narrower in HR than C mice. Paw contact area and duty factor were significantly greater in minimuscle individuals (subset of HR mice with 50%-reduced hind limb muscle mass) than in normal-muscled HR or C mice. We conclude that

Evidence for positive, but not negative, behavioral contrast with wheel-running reinforcement on multiple variable-ratio schedules.

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Belke, Terry W; Pierce, W David

2016-12-01

Rats responded on a multiple variable-ratio (VR) 10 VR 10 schedule of reinforcement in which lever pressing was reinforced by the opportunity to run in a wheel for 30s in both the changed (manipulated) and unchanged components. To generate positive contrast, the schedule of reinforcement in the changed component was shifted to extinction; to generate negative contrast, the schedule was shifted to VR 3. With the shift to extinction in the changed component, wheel-running and local lever-pressing rates increased in the unchanged component, a result supporting positive contrast; however, the shift to a VR 3 schedule in the changed component showed no evidence of negative contrast in the unaltered setting, only wheel running decreased in the unchanged component. Changes in wheel-running rates across components were consistent in showing a compensation effect, depending on whether the schedule manipulation increased or decreased opportunities for wheel running in the changed component. These findings are the first to demonstrate positive behavioral contrast on a multiple schedule with wheel running as reinforcement in both components. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of voluntary exercise on spontaneous physical activity and food consumption in mice: Results from an artificial selection experiment.

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Copes, Lynn E; Schutz, Heidi; Dlugosz, Elizabeth M; Acosta, Wendy; Chappell, Mark A; Garland, Theodore

2015-10-01

We evaluated the effect of voluntary exercise on spontaneous physical activity (SPA) and food consumption in mice from 4 replicate lines bred for 57 generations for high voluntary wheel running (HR) and from 4 non-selected control (C) lines. Beginning at ~24 days of age, mice were housed in standard cages or in cages with attached wheels. Wheel activity and SPA were monitored in 1-min intervals. Data from the 8th week of the experiment were analyzed because mice were sexually mature and had plateaued in body mass, weekly wheel running distance, SPA, and food consumption. Body mass, length, and masses of the retroperitoneal fat pad, liver, and heart were recorded after the 13th week. SPA of both HR and C mice decreased with wheel access, due to reductions in both duration and average intensity of SPA. However, total activity duration (SPA+wheel running; min/day) was ~1/3 greater when mice were housed with wheels, and food consumption was significantly increased. Overall, food consumption in both HR and C mice was more strongly affected by wheel running than by SPA. Duration of wheel running had a stronger effect than average speed, but the opposite was true for SPA. With body mass as a covariate, chronic wheel access significantly reduced fat pad mass and increased heart mass in both HR and C mice. Given that both HR and C mice housed with wheels had increased food consumption, the energetic cost of wheel running was not fully compensated by concomitant reductions in SPA. The experiment demonstrates that both duration and intensity of both wheel running and SPA were significant predictors of food consumption. This sort of detailed analysis of the effects of different aspects of physical activity on food consumption has not previously been reported for a non-human animal, and it sets the stage for longitudinal examination of energy balance and its components in rodent models. Copyright © 2015 Elsevier Inc. All rights reserved.

Investigation of pre-pubertal sex differences in wheel running and social behavior in three mouse strains.

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Gordon, Elizabeth A; Corbitt, Cynthia

2015-08-01

Sex differences in social behaviors exist in mammals during adulthood, and further evidence suggests that sex differences in behavior are present before sexual maturity. In order to model behavioral disorders in animals, it is important to assess baseline sex-related behavioral differences, especially when studying disorders for which sex-related behavioral effects are expected. We investigated the effect of sex on behavior in 3 strains of pre-pubertal mice (C57BL/6, CFW, and CF1) using a wheel-running assay. We found no significant sex differences in latency to run on the wheel or total duration of wheel running within each strain. During the social interaction test, there were no differences between sexes in latency or total duration of contact or following between a subject and novel mouse. We also evaluated behavioral patterns of wheel running and stereotypical behaviors, such as burrowing and grooming. Both sexes showed characteristic wheel running behavior, spending the majority of each trial interacting with the wheel when it was free and more time performing other activities ( e.g. , stereotypical behaviors, general locomotion) when it was jammed. These results provide evidence that, among various strains of pre-pubertal mice, baseline sex-related behavioral differences are not strong enough to influence the measured behaviors.

Decrease in Ground-Run Distance of Small Airplanes by Applying Electrically-Driven Wheels

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Kobayashi, Hiroshi; Nishizawa, Akira

A new takeoff method for small airplanes was proposed. Ground-roll performance of an airplane driven by electrically-powered wheels was experimentally and computationally studied. The experiments verified that the ground-run distance was decreased by half with a combination of the powered driven wheels and propeller without increase of energy consumption during the ground-roll. The computational analysis showed the ground-run distance of the wheel-driven aircraft was independent of the motor power when the motor capability exceeded the friction between tires and ground. Furthermore, the distance was minimized when the angle of attack was set to the value so that the wing generated negative lift.

Differential expression of stress proteins in rat myocardium after free wheel or treadmill run training.

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Noble, E G; Moraska, A; Mazzeo, R S; Roth, D A; Olsson, M C; Moore, R L; Fleshner, M

1999-05-01

High-intensity treadmill exercise increases the expression of a cardioprotective, inducible 72-kDa stress protein (SP72) in cardiac muscle. This investigation examined whether voluntary free wheel exercise training would be sufficient to confer a similar response. Male Sprague-Dawley rats were randomly assigned to either treadmill (TM-Tr) or free wheel (FW-Tr) training groups. By the end of the 8-wk training period, TM-Tr animals ran 1 h/day, 5 days/wk up a 10% grade, covering a distance of 8,282 m/wk. FW-Tr rats ran, on average, 5,300 m/wk, with one-third of the animals covering distances similar to those for the TM-Tr group. At the time of death, hearts of trained and caged sedentary control (Sed) animals were divided into left (LV) and right (RV) ventricles. Citrate synthase activity and the relative immunoblot contents of SP72, SP73 (the constitutive isoform of the SP70 family), and a 75-kDa mitochondrial chaperone (SP75) were subsequently determined. LV and RV did not differ on any measure, and SP73, SP75, and citrate synthase were not affected by training. Cardiac SP72 levels were elevated over fourfold in both ventricles of TM-Tr compared with RV of FW-Sed rats. Despite the animals having run a similar total distance, cardiac SP72 content in FW-Tr rats was not different from that in Sed animals. These data indicate that voluntary exercise training is insufficient to elicit an elevation of SP72 in rat heart and suggest that exercise intensity may be a critical factor in evoking the cardioprotective SP72 response.

Investigations of timing during the schedule and reinforcement intervals with wheel-running reinforcement.

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Belke, Terry W; Christie-Fougere, Melissa M

2006-11-01

Across two experiments, a peak procedure was used to assess the timing of the onset and offset of an opportunity to run as a reinforcer. The first experiment investigated the effect of reinforcer duration on temporal discrimination of the onset of the reinforcement interval. Three male Wistar rats were exposed to fixed-interval (FI) 30-s schedules of wheel-running reinforcement and the duration of the opportunity to run was varied across values of 15, 30, and 60s. Each session consisted of 50 reinforcers and 10 probe trials. Results showed that as reinforcer duration increased, the percentage of postreinforcement pauses longer than the 30-s schedule interval increased. On probe trials, peak response rates occurred near the time of reinforcer delivery and peak times varied with reinforcer duration. In a second experiment, seven female Long-Evans rats were exposed to FI 30-s schedules leading to 30-s opportunities to run. Timing of the onset and offset of the reinforcement period was assessed by probe trials during the schedule interval and during the reinforcement interval in separate conditions. The results provided evidence of timing of the onset, but not the offset of the wheel-running reinforcement period. Further research is required to assess if timing occurs during a wheel-running reinforcement period.

Influence of photoperiod and running wheel access on the entrainment of split circadian rhythms in hamsters

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Elliott Jeffrey A

2005-06-01

Full Text Available Abstract Background In the laboratory, behavioral and physiological states of nocturnal rodents alternate, with a period near 24 h, between those appropriate for the night (e.g., elevated wheel-running activity and high melatonin secretion and for the day (e.g., rest and low melatonin secretion. Under appropriate 24 h light:dark:light:dark conditions, however, rodents may be readily induced to express bimodal rest/activity cycles that reflect a global temporal reorganization of the central neural pacemaker in the hypothalamus. We examine here how the relative length of the light and dark phases of the environmental cycle influences this rhythm splitting and the necessity of a running wheel for expression of this entrainment condition. Results Rhythm splitting was observed in wheel-running and general locomotion of Siberian and Syrian hamsters. The latter also manifest split rhythms in body temperature. Access to a running wheel was necessary neither for the induction nor maintenance of this entrainment pattern. While rhythms were only transiently split in many animals with two 5 h nights, the incidence of splitting was greater with twice daily nights of shorter duration. Removal of running wheels altered the body temperature rhythm but did not eliminate its clear bimodality. Conclusion The expression of entrained, split circadian rhythms exhibits no strict dependence on access to a running wheel, but can be facilitated by manipulation of ambient lighting conditions. These circadian entrainment patterns may be of therapeutic value to human shift-workers and others facing chronobiological challenges.

Responding for sucrose and wheel-running reinforcement: effect of body weight manipulation.

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Belke, Terry W

2004-02-27

As body weight increases, the excitatory strength of a stimulus signaling an opportunity to run should weaken to a greater degree than that of a stimulus signaling an opportunity to eat. To test this hypothesis, six male albino Wistar rats were placed in running wheels and exposed to a fixed interval 30-s schedule that produced either a drop of 15% sucrose solution or the opportunity to run for 15s as reinforcing consequences for lever pressing. Each reinforcer type was signaled by a different stimulus. The effect of varying body weight on responding maintained by these two reinforcers was investigated by systematically increasing and decreasing post-session food amounts. The initial body weight was 335 g. Body weights were increased to approximately 445 g and subsequently returned to 335 g. As body weight increased, overall and local lever-pressing rates decreased while post-reinforcement pauses lengthened. Analysis of post-reinforcement pauses and local lever-pressing rates in terms of transitions between successive reinforcers revealed that local response rates in the presence of stimuli signaling upcoming wheel and sucrose reinforcers were similarly affected. However, pausing in the presence of the stimulus signaling a wheel-running reinforcer lengthened to a greater extent than did pausing in the presence of the stimulus signaling sucrose. This result suggests that as body weight approaches ad-lib levels, the likelihood of initiation of responding to obtain an opportunity to run approaches zero and the animal "rejects" the opportunity to run in a manner similar to the rejection of less preferred food items in studies of food selectivity.

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.

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Toedebusch, Ryan G; Ruegsegger, Gregory N; Braselton, Joshua F; Heese, Alexander J; Hofheins, John C; Childs, Tom E; Thyfault, John P; Booth, Frank W

2016-02-01

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. Copyright © 2016 the American Physiological Society.

Effects of Post-Session Wheel Running on Within-Session Changes in Operant Responding

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Aoyama, Kenjiro

2007-01-01

This study tested the effects of post-session wheel running on within-session changes in operant responding. Lever-pressing by six rats was reinforced by a food pellet under a continuous reinforcement (CRF) schedule in 30-min sessions. Two different flavored food pellets were used as reinforcers. In the wheel conditions, 30-min operant-sessions…

Sex differences in the effect of wheel running on subsequent nicotine-seeking in a rat adolescent-onset self-administration model

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Sanchez, Victoria; Moore, Catherine F; Brunzell, Darlene H; Lynch, Wendy J

2014-01-01

Rationale Wheel running attenuates nicotine-seeking in male adolescent rats; however it is not known if this effect extends to females. Objective To determine if wheel running during abstinence would differentially attenuate subsequent nicotine-seeking in male and female rats that had extended access to nicotine self-administration during adolescence. Methods Male (N = 49) and female (N = 43) adolescent rats self-administered saline or nicotine (5μg/kg) under an extended access (23-hour) paradigm. Following the last self-administration session, rats were moved to polycarbonate cages for an abstinence period where they either had access to a locked or unlocked running wheel for 2-hours/day. Subsequently, nicotine-seeking was examined under a within-session extinction/cue-induced reinstatement paradigm. Due to low levels of nicotine-seeking in females in both wheel groups, additional groups were included that were housed without access to a running wheel during abstinence. Results Females self-administered more nicotine as compared to males; however, within males and females, intake did not differ between groups prior to wheel assignment. Compared to saline controls, males and females that self-administered nicotine showed a significant increase in drug-seeking during extinction. Wheel running during abstinence attenuated nicotine-seeking during extinction in males. In females, access to either locked or unlocked wheels attenuated nicotine-seeking during extinction. While responding was reinstated by cues in both males and females, levels were modest and not significantly affected by exercise in this adolescent-onset model. Conclusions While wheel running reduced subsequent nicotine-seeking in males, access to a wheel, either locked or unlocked, was sufficient to suppress nicotine-seeking in females. PMID:24271035

Limits to sustained energy intake. XV. Effects of wheel running on the energy budget during lactation.

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Zhao, Zhi-Jun; Król, Elzbieta; Moille, Sophie; Gamo, Yuko; Speakman, John R

2013-06-15

The capacity of animals to dissipate heat may constrain sustained energy intake during lactation. We examined these constraints at peak lactation in MF1 mice that had ad libitum access to food, or that had to run a pre-set target on running wheels to obtain ad libitum access to food. The voluntary distance run decreased sharply during pregnancy and peak lactation. When lactating females were provided with 80% of their estimated food requirements, and had to run pre-set distances of 2, 4 or 6 km before given access to additional ad libitum food, most of them did not complete the running target during late lactation and the mice with the highest targets failed to reach their targets earlier in lactation. There were consequently significant group differences in asymptotic food intake (2 km, 16.97 ± 0.40 g day(-1); 4 km, 14.29 ± 0.72 g day(-1); and 6 km, 12.65 ± 0.45 g day(-1)) and weaned litter masses (2 km, 71.11 ± 2.39 g; 4 km, 54.63 ± 4.28 g and 6 km, 47.18 ± 2.46 g). When the females did run sufficiently to gain ad libitum food access, their intake did not differ between the different distance groups or from controls that were not required to run. Thus, despite being physically capable of running the distances, mice could not exercise sufficiently in lactation to gain regular ad libitum access to food, probably because of the risks of hyperthermia when combining heat production from exercise with thermogenesis from lactation.

Voluntary Exercise Improves Estrous Cyclicity in Prenatally Androgenized Female Mice Despite Programming Decreased Voluntary Exercise: Implications for Polycystic Ovary Syndrome (PCOS).

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Homa, Lori D; Burger, Laura L; Cuttitta, Ashley J; Michele, Daniel E; Moenter, Suzanne M

2015-12-01

Prenatal androgen (PNA) exposure in mice produces a phenotype resembling lean polycystic ovary syndrome. We studied effects of voluntary exercise on metabolic and reproductive parameters in PNA vs vehicle (VEH)-treated mice. Mice (8 wk of age) were housed individually and estrous cycles monitored. At 10 weeks of age, mice were divided into groups (PNA, PNA-run, VEH, VEH-run, n = 8-9/group); those in the running groups received wheels allowing voluntary running. Unexpectedly, PNA mice ran less distance than VEH mice; ovariectomy eliminated this difference. In ovary-intact mice, there was no difference in glucose tolerance, lower limb muscle fiber types, weight, or body composition among groups after 16 weeks of running, although some mitochondrial proteins were mildly up-regulated by exercise in PNA mice. Before running, estrous cycles in PNA mice were disrupted with most days in diestrus. There was no change in cycles during weeks 1-6 of running (10-15 wk of age). In contrast, from weeks 11 to 16 of running, cycles in PNA mice improved with more days in proestrus and estrus and fewer in diestrus. PNA programs reduced voluntary exercise, perhaps mediated in part by ovarian secretions. Exercise without weight loss improved estrous cycles, which if translated could be important for fertility in and counseling of lean women with polycystic ovary syndrome.

Home cage wheel running is an objective and clinically relevant method to assess inflammatory pain in male and female rats

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Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Background The assessment of nociception in preclinical studies is undergoing a transformation from pain-evoked to pain-depressed tests to more closely mimic the effects of clinical pain. Many inflammatory pain-depressed behaviors (reward seeking, locomotion) have been examined, but these tests are limited because of confounds such as stress and difficulties in quantifying behavior. New Method The present study evaluates home cage wheel running as an objective method to assess the magnitude and duration of inflammatory pain in male and female rats. Results Injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw to induce inflammatory pain almost completely inhibited wheel running for 2 days in males and females. Wheel running gradually returned to baseline levels within 12 days despite persistent mechanical hypersensitivity (von Frey test). Comparison with Existing Methods Continuously monitoring home cage wheel running improves on previous studies examining inflammatory pain-depressed wheel running because it is more sensitive to noxious stimuli, avoids the stress of removing the rat from its cage for testing, and provides a complete analysis of the time course for changes in nociception. Conclusions The present data indicate that home cage wheel running is a clinically relevant method to assess inflammatory pain in the rat. The decrease in activity caused by inflammatory pain and subsequent gradual recovery mimics the changes in activity caused by pain in humans. The tendency for pain-depressed wheel running to be greater in female than male rats is consistent with the tendency for women to be at greater risk of chronic pain than men. PMID:26891874

Techniques for establishing schedules with wheel running as reinforcement in rats.

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Iversen, I H

1993-07-01

In three experiments, access to wheel running was contingent on lever pressing. In each experiment, the duration of access to running was reduced gradually to 4, 5, or 6 s, and the schedule parameters were expanded gradually. The sessions lasted 2 hr. In Experiment 1, a fixed-ratio 20 schedule controlled a typical break-and-run pattern of lever pressing that was maintained throughout the session for 3 rats. In Experiment 2, a fixed-interval schedule of 6 min maintained lever pressing throughout the session for 3 rats, and for 1 rat, the rate of lever pressing was positively accelerated between reinforcements. In Experiment 3, a variable-ratio schedule of 20 or 35 was in effect and maintained lever pressing at a very stable pace throughout the session for 2 of 3 rats; for 1 rat, lever pressing was maintained at an irregular rate. When the session duration was extended to successive 24-hr periods, with food and water accessible in Experiment 3, lever pressing settled into a periodic pattern occurring at a high rate at approximately the same time each day. In each experiment, the rats that developed the highest local rates of running during wheel access also maintained the most stable and highest rates of lever pressing.

Spontaneous appetence for wheel-running: a model of dependency on physical activity in rat.

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Ferreira, Anthony; Lamarque, Stéphanie; Boyer, Patrice; Perez-Diaz, Fernando; Jouvent, Roland; Cohen-Salmon, Charles

2006-12-01

According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Forward conditioning with wheel running causes place aversion in rats.

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Masaki, Takahisa; Nakajima, Sadahiko

2008-09-01

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.

Voluntary exercise does not ameliorate context memory and hyperarousal in a mouse model for post-traumatic stress disorder (PTSD).

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Cacciaglia, Raffaele; Krause-Utz, Annegret; Vogt, Miriam A; Schmahl, Christian; Flor, Herta; Gass, Peter

2013-07-01

We investigated the effects of voluntary wheel running as model for intervention on the development of contextual fear and hyperarousal in a mouse model of post-traumatic stress disorder (PTSD). Physical exercise in general has been associated with improved hippocampus-dependent memory performance both in animals and humans. However, studies that have tried to link physical exercise and contextual conditioning in an animal model of PTSD, revealed mixed findings. Here we tested contextual fear conditioning, generalized fear response, acoustic startle response and emotionality in C57BL/6NCrl mice which had free access to a running wheel for 28 days, compared with control animals which did not run and mice which did not receive a shock during the conditioning phase. We found no significant effects of voluntary running on the above-mentioned variables, except for enhanced anxiety levels in the Dark-Light-Box and O-Maze tests of running mice. Our results suggest that running as a model for intervention does not ameliorate contextual aversive learning but has the potency to change emotional behaviours.

Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats.

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Yau, S-Y; Lau, B W-M; Zhang, E-D; Lee, J C-D; Li, A; Lee, T M C; Ching, Y-P; Xu, A-M; So, K-F

2012-10-11

Previous studies have shown that a 2-week treatment with 40 mg/kg corticosterone (CORT) in rats suppresses hippocampal neurogenesis and decreases hippocampal brain-derived neurotrophic factor (BDNF) levels and impairs spatial learning, all of which could be counteracted by voluntary wheel running. BDNF and insulin-like growth factor (IGF-1) have been suggested to mediate physical exercise-enhanced hippocampal neurogenesis and cognition. Here we examined whether such running-elicited benefits were accompanied by corresponding changes of peripheral BDNF and IGF-1 levels in a rat model of stress. We examined the effects of acute (5 days) and chronic (4 weeks) treatment with CORT and/or wheel running on (1) hippocampal cell proliferation, (2) spatial learning and memory and (3) plasma levels of BDNF and IGF-1. Acute CORT treatment improved spatial learning without altered cell proliferation compared to vehicle treatment. Acute CORT-treated non-runners showed an increased trend in plasma BDNF levels together with a significant increase in hippocampal BDNF levels. Acute running showed no effect on cognition, cell proliferation and peripheral BDNF and IGF-1 levels. Conversely, chronic CORT treatment in non-runners significantly impaired spatial learning and suppressed cell proliferation in association with a decreased trend in plasma BDNF level and a significant increase in hippocampal BDNF levels. Running counteracted cognitive deficit and restored hippocampal cell proliferation following chronic CORT treatment; but without corresponding changes in plasma BDNF and IGF-1 levels. The results suggest that the beneficial effects of acute stress on cognitive improvement may be mediated by BDNF-enhanced synaptic plasticity that is hippocampal cell proliferation-independent, whereas chronic stress may impair cognition by decreasing hippocampal cell proliferation and BDNF levels. Furthermore, the results indicate a trend in changes of plasma BDNF levels associated with a

Effect of voluntary physical activity initiated at age 7 months on skeletal hindlimb and cardiac muscle function in mdx mice of both genders.

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Ferry, Arnaud; Benchaouir, Rachid; Joanne, Pierre; Peat, Rachel A; Mougenot, Nathalie; Agbulut, Onnik; Butler-Browne, Gillian

2015-11-01

The effects of voluntary activity initiated in adult mdx (C57BL/10ScSc-DMD(mdx) /J) mice on skeletal and cardiac muscle function have not been studied extensively. We studied the effects of 3 months of voluntary wheel running initiated at age 7 months on hindlimb muscle weakness, increased susceptibility to muscle contraction-induced injury, and left ventricular function in mdx mice. We found that voluntary wheel running did not worsen the deficit in force-generating capacity and the force drop after lengthening contractions in either mdx mouse gender. It increased the absolute maximal force of skeletal muscle in female mdx mice. Moreover, it did not affect left ventricular function, structural heart dimensions, cardiac gene expression of inflammation, fibrosis, or remodeling markers. These results indicate that voluntary activity initiated at age 7 months had no detrimental effects on skeletal or cardiac muscles in either mdx mouse gender. © 2015 Wiley Periodicals, Inc.

Effects of selective breeding for increased wheel-running behavior on circadian timing of substrate oxidation and ingestive behavior.

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Jónás, I; Vaanholt, L M; Doornbos, M; Garland, T; Scheurink, A J W; Nyakas, C; van Dijk, G

2010-04-19

Fluctuations in substrate preference and utilization across the circadian cycle may be influenced by the degree of physical activity and nutritional status. In the present study, we assessed these relationships in control mice and in mice from a line selectively bred for high voluntary wheel-running behavior, either when feeding a carbohydrate-rich/low-fat (LF) or a high-fat (HF) diet. Housed without wheels, selected mice, and in particular the females, exhibited higher cage activity than their non-selected controls during the dark phase and at the onset of the light phase, irrespective of diet. This was associated with increases in energy expenditure in both sexes of the selection line. In selected males, carbohydrate oxidation appeared to be increased compared to controls. In contrast, selected females had profound increases in fat oxidation above the levels in control females to cover the increased energy expenditure during the dark phase. This is remarkable in light of the finding that the selected mice, and in particular the females showed higher preference for the LF diet relative to controls. It is likely that hormonal and/or metabolic signals increase carbohydrate preference in the selected females, which may serve optimal maintenance of cellular metabolism in the presence of augmented fat oxidation. (c) 2010 Elsevier Inc. All rights reserved.

Therapy of solid cancers using T cells and running shoes

DEFF Research Database (Denmark)

Straten, Per Thor

2017-01-01

of tumor specific T cells at the tumor site, and underscores the need to define ways as how to increase immune cell infiltration to the tumor site. Regular exercise reduces the risk of cancer and disease recurrence, by largely unknown mechanisms. We recently demonstrated that voluntary wheel running showed...

Voluntary and forced exercise influence the survival and body composition of ageing male rats differently.

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Narath, E; Skalicky, M; Viidik, A

2001-11-01

The importance of maintaining physical fitness by engaging in exercise in a life-long perspective as well as the avoidance of obesity has been emphasised in recent years by epidemiological studies on human populations as well as studies on laboratory rodents. In laboratory studies, voluntary running in wheels and forced training in a treadmill have been used with beneficial results. Restriction of the food intake of sedentary laboratory rodents can be regarded either as life prolongation or prevention of life shortening by obesity. We compared the effects of these interventions on male Sprague-Dawley rats from the age of 5 to 23 months in the following groups: (1) RW=voluntary running in wheels; (2) PW=fed to pair weight with RW animals; (3) TM=forced training in a treadmill; and (4) S1=sedentary with ad libitum access to food. Each group consisted of 32 animals, all housed individually in cages. Two RW animals died, five died in each of the PW and S1 groups and 10 in the TM group (pmuch they run.

Effect of sucrose availability on wheel-running as an operant and as a reinforcing consequence on a multiple schedule: Additive effects of extrinsic and automatic reinforcement.

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Belke, Terry W; Pierce, W David

2015-07-01

As a follow up to Belke and Pierce's (2014) study, we assessed the effects of repeated presentation and removal of sucrose solution on the behavior of rats responding on a two-component multiple schedule. Rats completed 15 wheel turns (FR 15) for either 15% or 0% sucrose solution in the manipulated component and lever pressed 10 times on average (VR 10) for an opportunity to complete 15 wheel turns (FR 15) in the other component. In contrast to our earlier study, the components advanced based on time (every 8min) rather than completed responses. Results showed that in the manipulated component wheel-running rates were higher and the latency to initiate running longer when sucrose was present (15%) compared to absent (0% or water); the number of obtained outcomes (sucrose/water), however, did not differ with the presentation and withdrawal of sucrose. For the wheel-running as reinforcement component, rates of wheel turns, overall lever-pressing rates, and obtained wheel-running reinforcements were higher, and postreinforcement pauses shorter, when sucrose was present (15%) than absent (0%) in manipulated component. Overall, our findings suggest that wheel-running rate regardless of its function (operant or reinforcement) is maintained by automatically generated consequences (automatic reinforcement) and is increased as an operant by adding experimentally arranged sucrose reinforcement (extrinsic reinforcement). This additive effect on operant wheel-running generalizes through induction or arousal to the wheel-running as reinforcement component, increasing the rate of responding for opportunities to run and the rate of wheel-running per opportunity. Copyright © 2015 Elsevier B.V. All rights reserved.

Running wheel exercise before a binge regimen of methamphetamine does not protect against striatal dopaminergic damage.

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O'dell, Steven J; Marshall, John F

2014-09-01

Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic nerve terminals as measured by decreases in tissue dopamine (DA) content and levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell bodies from which the DA terminals arise survive, and previous reports show that striatal DA markers return to control levels by 12 months post-mAMPH, suggesting long-term repair or regrowth of damaged DA terminals. We previously showed that when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced decreases in striatal DAT. However, these data left unresolved the question of whether exercise protected against the initial neurotoxicity from the mAMPH binge or accelerated the repair of the damaged DA terminals. The present experiments were designed to test whether exercise protects against the mAMPH-induced injury. Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an additional week before autoradiographic determination of striatal DAT binding. The autoradiographic findings showed that prior exercise provided no protection against mAMPH-induced damage to striatal DA terminals. These results, together with analyses from our previous experiments, suggest that voluntary exercise may accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise may be useful as therapeutic adjunct in the treatment mAMPH addicts. © 2014 Wiley Periodicals, Inc.

Depression of home cage wheel running is an objective measure of spontaneous morphine withdrawal in rats with and without persistent pain

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Kandasamy, Ram; Lee, Andrea T.; Morgan, Michael M.

2017-01-01

Opioid withdrawal in humans is often subtle and almost always spontaneous. In contrast, most preclinical studies precipitate withdrawal by administration of an opioid receptor antagonist such as naloxone. These animal studies rely on measurement of physiological symptoms (e.g., wet dog shakes) in the period immediately following naloxone administration. To more closely model the human condition, we tested the hypothesis that depression of home cage wheel running will provide an objective method to measure the magnitude and duration of spontaneous morphine withdrawal. Rats were allowed access to a running wheel in their home cage for 8 days prior to implantation of two 75 mg morphine or placebo pellets. The pellets were removed 3 or 5 days later to induce spontaneous withdrawal. In normal pain-free rats, removal of the morphine pellets depressed wheel running for 48 hours compared to rats that had placebo pellets removed. Morphine withdrawal-induced depression of wheel running was greatly enhanced in rats with persistent inflammatory pain induced by injection of Complete Freund’s Adjuvant (CFA) into the hindpaw. Removal of the morphine pellets following 3 days of treatment depressed wheel running in these rats for over 6 days. These data demonstrate that home cage wheel running provides an objective and more clinically relevant method to assess spontaneous morphine withdrawal compared to precipitated withdrawal in laboratory rats. Moreover, the enhanced withdrawal in rats with persistent inflammatory pain suggests that pain patients may be especially susceptible to opioid withdrawal. PMID:28366799

Simple and conditional visual discrimination with wheel running as reinforcement in rats.

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Iversen, I H

1998-09-01

Three experiments explored whether access to wheel running is sufficient as reinforcement to establish and maintain simple and conditional visual discriminations in nondeprived rats. In Experiment 1, 2 rats learned to press a lit key to produce access to running; responding was virtually absent when the key was dark, but latencies to respond were longer than for customary food and water reinforcers. Increases in the intertrial interval did not improve the discrimination performance. In Experiment 2, 3 rats acquired a go-left/go-right discrimination with a trial-initiating response and reached an accuracy that exceeded 80%; when two keys showed a steady light, pressing the left key produced access to running whereas pressing the right key produced access to running when both keys showed blinking light. Latencies to respond to the lights shortened when the trial-initiation response was introduced and became much shorter than in Experiment 1. In Experiment 3, 1 rat acquired a conditional discrimination task (matching to sample) with steady versus blinking lights at an accuracy exceeding 80%. A trial-initiation response allowed self-paced trials as in Experiment 2. When the rat was exposed to the task for 19 successive 24-hr periods with access to food and water, the discrimination performance settled in a typical circadian pattern and peak accuracy exceeded 90%. When the trial-initiation response was under extinction, without access to running, the circadian activity pattern determined the time of spontaneous recovery. The experiments demonstrate that wheel-running reinforcement can be used to establish and maintain simple and conditional visual discriminations in nondeprived rats.

Access to a running wheel inhibits the acquisition of cocaine self-administration.

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Smith, Mark A; Pitts, Elizabeth G

2011-12-01

Physical activity decreases cocaine self-administration in laboratory animals and is associated with positive outcomes in substance abuse treatment programs; however, less is known about its efficacy in preventing the establishment of regular patterns of substance use in drug-naive individuals. The purpose of the present study was to examine the effects of access to a running wheel on the acquisition of cocaine self-administration in experimentally naive rats. Male, Long-Evans rats were obtained at weaning and assigned to sedentary (no wheel) or exercising (access to wheel) conditions immediately upon arrival. After six weeks, rats were surgically implanted with intravenous catheters and placed in operant conditioning chambers for 2 h/day for 15 consecutive days. Each session began with a noncontingent priming infusion of cocaine, followed by a free-operant period in which each response on the active lever produced an infusion of cocaine on a fixed ratio (FR1) schedule of reinforcement. For days 1-5, responding was reinforced with 0.25 mg/kg/infusion cocaine; for days 6-15, responding was reinforced with 0.75 mg/kg/infusion cocaine. In addition, all rats were calorically restricted during days 11-15 to 85% to 95% of their free-feeding body weight. Compared to sedentary rats, exercising rats acquired cocaine self-administration at a significantly slower rate and emitted significantly fewer active lever presses during the 15 days of behavioral testing. These data indicate that access to a running wheel inhibits the acquisition of cocaine self-administration, and that physical activity may be an effective intervention in substance abuse prevention programs. Copyright © 2011 Elsevier Inc. All rights reserved.

Agomelatine, venlafaxine, and running exercise effectively prevent anxiety- and depression-like behaviors and memory impairment in restraint stressed rats.

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Sarawut Lapmanee

Full Text Available Several severe stressful situations, e.g., natural disaster, infectious disease out break, and mass casualty, are known to cause anxiety, depression and cognitive impairment, and preventive intervention for these stress complications is worth exploring. We have previously reported that the serotonin-norepinephrine-dopamine reuptake inhibitor, venlafaxine, as well as voluntary wheel running are effective in the treatment of anxiety- and depression-like behaviors in stressed rats. But whether they are able to prevent deleterious consequences of restraint stress in rats, such as anxiety/depression-like behaviors and memory impairment that occur afterward, was not known. Herein, male Wistar rats were pre-treated for 4 weeks with anti-anxiety/anti-depressive drugs, agomelatine and venlafaxine, or voluntary wheel running, followed by 4 weeks of restraint-induced stress. During the stress period, rats received neither drug nor exercise intervention. Our results showed that restraint stress induced mixed anxiety- and depression-like behaviors, and memory impairment as determined by elevated plus-maze, elevated T-maze, open field test (OFT, forced swimming test (FST, and Morris water maze (MWM. Both pharmacological pre-treatments and running successfully prevented the anxiety-like behavior, especially learned fear, in stressed rats. MWM test suggested that agomelatine, venlafaxine, and running could prevent stress-induced memory impairment, but only pharmacological treatments led to better novel object recognition behavior and positive outcome in FST. Moreover, western blot analysis demonstrated that venlafaxine and running exercise upregulated brain-derived neurotrophic factor (BDNF expression in the hippocampus. In conclusion, agomelatine, venlafaxine as well as voluntary wheel running had beneficial effects, i.e., preventing the restraint stress-induced anxiety/depression-like behaviors and memory impairment.

Effects of long-term voluntary exercise on learning and memory processes: dependency of the task and level of exercise.

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García-Capdevila, Sílvia; Portell-Cortés, Isabel; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David

2009-09-14

The effect of long-term voluntary exercise (running wheel) on anxiety-like behaviour (plus maze and open field) and learning and memory processes (object recognition and two-way active avoidance) was examined on Wistar rats. Because major individual differences in running wheel behaviour were observed, the data were analysed considering the exercising animals both as a whole and grouped according to the time spent in the running wheel (low, high, and very-high running). Although some variables related to anxiety-like behaviour seem to reflect an anxiogenic compatible effect, the view of the complete set of variables could be interpreted as an enhancement of defensive and risk assessment behaviours in exercised animals, without major differences depending on the exercise level. Effects on learning and memory processes were dependent on task and level of exercise. Two-way avoidance was not affected either in the acquisition or in the retention session, while the retention of object recognition task was affected. In this latter task, an enhancement in low running subjects and impairment in high and very-high running animals were observed.

Voluntary Exercise Training: Analysis of Mice in Uninjured, Inflammatory, and Nerve-Injured Pain States.

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Tayler D Sheahan

Full Text Available Both clinical and animal studies suggest that exercise may be an effective way to manage inflammatory and neuropathic pain conditions. However, existing animal studies commonly use forced exercise paradigms that incorporate varying degrees of stress, which itself can elicit analgesia, and thus may complicate the interpretation of the effects of exercise on pain. We investigated the analgesic potential of voluntary wheel running in the formalin model of acute inflammatory pain and the spared nerve injury model of neuropathic pain in mice. In uninjured, adult C57BL/6J mice, 1 to 4 weeks of exercise training did not alter nociceptive thresholds, lumbar dorsal root ganglia neuronal excitability, or hindpaw intraepidermal innervation. Further, exercise training failed to attenuate formalin-induced spontaneous pain. Lastly, 2 weeks of exercise training was ineffective in reversing spared nerve injury-induced mechanical hypersensitivity or in improving muscle wasting or hindpaw denervation. These findings indicate that in contrast to rodent forced exercise paradigms, short durations of voluntary wheel running do not improve pain-like symptoms in mouse models of acute inflammation and peripheral nerve injury.

The Running Wheel Enhances Food Anticipatory Activity: An Exploratory Study

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Flôres, Danilo E. F. L.; Bettilyon, Crystal N.; Jia, Lori; Yamazaki, Shin

2016-01-01

Rodents anticipate rewarding stimuli such as daily meals, mates, and stimulant drugs. When a single meal is provided daily at a fixed time of day, an increase in activity, known as food anticipatory activity (FAA), occurs several hours before feeding time. The factors affecting the expression of FAA have not been well-studied. Understanding these factors may provide clues to the undiscovered anatomical substrates of food entrainment. In this study we determined whether wheel-running activity,...

Contingency discriminability and the generalized matching law describe choice on concurrent ratio schedules of wheel-running reinforcement.

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Belke, Terry W

2012-07-01

Belke (2010) showed that on concurrent ratio schedules, the difference in ratio requirements required to produce near exclusive preference for the lower ratio alternative was substantively greater when the reinforcer was wheel running than when it was sucrose. The current study replicated this finding and showed that this choice behavior can be described by the matching law and the contingency discriminability model. Eight female Long Evans rats were exposed to concurrent VR schedules of wheel-running reinforcement (30s) and the schedule value of the initially preferred alternative was systematically increased. Two rats rapidly developed exclusive preference for the lower ratio alternative, but the majority did not - even when ratios differed by 20:1. Analysis showed that estimates of slopes from the matching law and the proportion of reinforcers misattributed from the contingency discriminability model were related to the ratios at which near exclusive preference developed. The fit of these models would be consistent with misattribution of reinforcers or poor discrimination between alternatives due to the long duration of wheel running. Copyright © 2012 Elsevier B.V. All rights reserved.

The general matching law describes choice on concurrent variable-interval schedules of wheel-running reinforcement.

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Belke, T W; Belliveau, J

2001-05-01

Six male Wistar rats were exposed to concurrent variable-interval schedules of wheel-running reinforcement. The reinforcer associated with each alternative was the opportunity to run for 15 s, and the duration of the changeover delay was 1 s. Results suggested that time allocation was more sensitive to relative reinforcement rate than was response allocation. For time allocation, the mean slopes and intercepts were 0.82 and 0.008, respectively. In contrast, for response allocation, mean slopes and intercepts were 0.60 and 0.03, respectively. Correction for low response rates and high rates of changing over, however, increased slopes for response allocation to about equal those for time allocation. The results of the present study suggest that the two-operant form of the matching law can be extended to wheel-running reinforcement. 'I'he effects of a low overall response rate, a short Changeover delay, and long postreinforcement pausing on the assessment of matching in the present study are discussed.

Determination of vertical pressures on running wheels of freight trolleys of bridge type cranes

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Goncharov, K. A.; Denisov, I. A.

2018-03-01

The problematic issues of the design of the bridge-type trolley crane, connected with ensuring uniform load distribution between the running wheels, are considered. The shortcomings of the existing methods of calculation of reference pressures are described. The results of the analytical calculation of the pressure of the support wheels are compared with the results of the numerical solution of this problem for various schemes of trolley supporting frames. Conclusions are given on the applicability of various methods for calculating vertical pressures, depending on the type of metal structures used in the trolley.

Why Animals Run on Legs, Not on Wheels.

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Diamond, Jared

1983-01-01

Speculates why animals have not developed wheels in place of inefficient legs. One study cited suggests three reasons why animals are better off without wheels: wheels are efficient only on hard surfaces, limitation of wheeled motion due to vertical obstructions, and the problem of turning in spaces cluttered with obstacles. (JN)

Voluntary exercise increases cholesterol efflux but not macrophage reverse cholesterol transport in vivo in mice

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Kuipers Folkert

2010-07-01

Full Text Available Abstract Physical exercise beneficially impacts on the plasma lipoprotein profile as well as on the incidence of cardiovascular events and is therefore recommended in primary and secondary prevention strategies against atherosclerotic cardiovascular disease. However, the underlying mechanisms of the protective effect of exercise remain largely unknown. Therefore, the present study tested the hypothesis that voluntary exercise in mice impacts on cholesterol efflux and in vivo reverse cholesterol transport (RCT. After two weeks of voluntary wheel running (average 10.1 ± 1.4 km/day plasma triglycerides were lower (p

Analysis of inflammation-induced depression of home cage wheel running in rats reveals the difference between opioid antinociception and restoration of function

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Kandasamy, Ram; Calsbeek, Jonas J.; Morgan, Michael M.

2016-01-01

Opioids are effective at inhibiting responses to noxious stimuli in rodents, but have limited efficacy and many side effects in chronic pain patients. One reason for this disconnect is that nociception is typically assessed using withdrawal from noxious stimuli in animals, whereas chronic pain patients suffer from abnormal pain that disrupts normal activity. We hypothesized that assessment of home cage wheel running in rats would provide a much more clinically relevant method to assess opioid efficacy to restore normal behavior. Intraplantar injection of Complete Freund’s Adjuvant (CFA) into the right hindpaw depressed wheel running and caused mechanical allodynia measured with the von Frey test in both male and female rats. Administration of an ED50 dose of morphine (3.2 mg/kg) reversed mechanical allodynia, but did not reverse CFA-induced depression of wheel running. In contrast, administration of a low dose of morphine (1.0 mg/kg) restored running for one hour in both sexes, but had no effect on mechanical allodynia. Administration of the atypical opioid buprenorphine had no effect on inflammation-induced depression of wheel running in male or female rats, but attenuated mechanical allodynia in male rats. Administration of buprenorphine and higher doses of morphine depressed wheel running in non-inflamed rats, suggesting that the side effects of opioids interfere with restoration of function. These data indicate that restoration of pain-depressed function requires antinociception in the absence of disruptive side effects. The disruptive side effects of opioids are consistent with the major limitation of opioid use in human pain patients. PMID:27746208

Wheel set run profile renewing method effectiveness estimation

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Somov, Dmitrij; Bazaras, Žilvinas; Žukauskaite, Orinta

2010-01-01

At all the repair enterprises, despite decreased rim wear-off resistance, after every grinding only geometry wheel profile parameters are renewed. Exploit wheel rim work edge decrease tendency is noticed what induces acquiring new wheels. This is related to considerable axle load and train speed increase and also because of wheel work edge repair method imperfection.

Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats

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Sanchez, Victoria; Moore, Catherine F; Brunzell, Darlene H; Lynch, Wendy J

2013-01-01

Rationale Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. Objectives To determine if wheel running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. Methods Male adolescent rats (n = 55) were trained to self-administer saline or nicotine infusions (5 or 10 μg/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23-hr/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2-hr/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. Results Intake was higher at the 10 μg/kg dose as compared to the 5 μg/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest, but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. Conclusions Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction. PMID:23371488

Myosin heavy chain isoform expression in adult and juvenile mini-muscle mice bred for high-voluntary wheel running.

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Talmadge, Robert J; Acosta, Wendy; Garland, Theodore

2014-11-01

The myosin heavy chain (MyHC) isoform composition of locomotor and non-locomotor muscles of mini-muscle mice were assessed at the protein and mRNA levels in both adult and juvenile (21 day old) mice. Mini-muscle mice are one outcome of a replicated artificial selection experiment in which four lines of mice were bred for high voluntary wheel running (HR lines). Two of the lines responded with an increase in frequency of a single nucleotide polymorphism in an intron in the MyHC-2b gene (myh4) that when homozygous causes a dramatic reduction in triceps surae mass. We found that both locomotor and non-locomotor muscles of adult mini-muscle mice displayed robust reductions, but not elimination, of the MyHC-2b isoform at both the protein and mRNA levels, with commensurate increases in MyHC-2x and sometimes MyHC-2a, as compared with either a line of HR mice that does not display the mini-muscle phenotype or inbred C57Bl6 mice. Immunohistochemical analyses revealed that locomotor muscles of mini-muscle mice contain fibers that express the MyHC-2b isoform, which migrates normally in SDS-PAGE gels. However, these MyHC-2b positive fibers are generally smaller than the surrounding fibers and smaller than the MyHC-2b positive fibers of non-mini-muscle mice, resulting in characteristically fast muscles that lack a substantial MyHC-2b positive (superficial) region. In contrast, the masseter, a non-locomotor muscle of mini-muscle mice contained MyHC-2b positive fibers that stained more lightly for MyHC-2b, but appeared normal in size and distribution. In adults, many of the MyHC-2b positive fibers in the mini-muscle mice also display central nuclei. Only a small proportion of small MyHC-2b fibers in mini-muscle mice stained positive for the neural cell adhesion molecule, suggesting that anatomical innervation was not compromised. In addition, weanling (21 day old), but not 5 day old mice, displayed alterations in MyHC isoform content at both the protein and mRNA levels, including

Altered fibre types in gastrocnemius muscle of high wheel-running selected mice with mini-muscle phenotypes.

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Guderley, Helga; Joanisse, Denis R; Mokas, Sophie; Bilodeau, Geneviève M; Garland, Theodore

2008-03-01

Selective breeding of mice for high voluntary wheel running has favoured characteristics that facilitate sustained, aerobically supported activity, including a "mini-muscle" phenotype with markedly reduced hind limb muscle mass, increased mass-specific activities of oxidative enzymes, decreased % myosin heavy chain IIb, and, in the medial gastrocnemius, reduced twitch speed, reduced mass-specific isotonic power, and increased fatigue resistance. To evaluate whether selection has altered fibre type expression in mice with either "mini" or normal muscle phenotypes, we examined fibre types of red and white gastrocnemius. In both the medial and lateral gastrocnemius, the mini-phenotype increased activities of oxidative enzymes and decreased activities of glycolytic enzymes. In red muscle samples, the mini-phenotype markedly changed fibre types, with the % type I and type IIA fibres and the surface area of type IIA fibres increasing; in addition, mice from selected lines in general had an increased % type IIA fibres and larger type I fibres as compared with mice from control lines. White muscle samples from mini-mice showed dramatic structural alterations, with an atypical distribution of extremely small, unidentifiable fibres surrounded by larger, more oxidative fibres than normally present in white muscle. The increased proportion of oxidative fibres and these atypical small fibres together may explain the reduced mass and increased mitochondrial enzyme activities in mini-muscles. These and previous results demonstrate that extension of selective breeding beyond the time when the response of the selected trait (i.e. distance run) has levelled off can still modify the mechanistic underpinnings of this behaviour.

Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice.

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He, Xiao-Fei; Liu, Dong-Xu; Zhang, Qun; Liang, Feng-Ying; Dai, Guang-Yan; Zeng, Jin-Sheng; Pei, Zhong; Xu, Guang-Qing; Lan, Yue

2017-01-01

Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood-brain barrier (BBB) or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF) and the interstitial fluid (ISF). A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer's disease (AD), but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear. In this study, glymphatic clearance and BBB permeability were evaluated in aged mice using in vivo two-photon imaging. The mice performed voluntary wheel running exercise and their water-maze cognition was assessed; the expression of the astrocytic water channel aquaporin 4 (AQP4), astrocyte and microglial activation, and the accumulation of amyloid beta (Aβ) were evaluated with immunofluorescence or an enzyme-linked immunosorbent assay (ELISA); synaptic function was investigated with Thy1 -green fluorescent protein (GFP) transgenic mice and immunofluorescent staining. Voluntary wheel running significantly improved water-maze cognition in the aged mice, accelerated the efficiency of glymphatic clearance, but which did not affect BBB permeability. The numbers of activated astrocytes and microglia decreased, AQP4 expression increased, and the distribution of astrocytic AQP4 was rearranged. Aβ accumulation decreased, whereas dendrites, dendritic spines and postsynaptic density protein (PSD95) increased. Our study suggests that voluntary wheel running accelerated glymphatic clearance but not BBB permeation, improved astrocytic AQP4 expression and polarization, attenuated the accumulation of amyloid plaques and neuroinflammation, and ultimately protected mice against synaptic dysfunction and a decline in spatial cognition. These data suggest

Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice

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Xiao-fei He

2017-05-01

Full Text Available Age is characterized by chronic inflammation, leading to synaptic dysfunction and dementia because the clearance of protein waste is reduced. The clearance of proteins depends partly on the permeation of the blood–brain barrier (BBB or on the exchange of water and soluble contents between the cerebrospinal fluid (CSF and the interstitial fluid (ISF. A wealth of evidence indicates that physical exercise improves memory and cognition in neurodegenerative diseases during aging, such as Alzheimer’s disease (AD, but the influence of physical training on glymphatic clearance, BBB permeability and neuroinflammation remains unclear. In this study, glymphatic clearance and BBB permeability were evaluated in aged mice using in vivo two-photon imaging. The mice performed voluntary wheel running exercise and their water-maze cognition was assessed; the expression of the astrocytic water channel aquaporin 4 (AQP4, astrocyte and microglial activation, and the accumulation of amyloid beta (Aβ were evaluated with immunofluorescence or an enzyme-linked immunosorbent assay (ELISA; synaptic function was investigated with Thy1–green fluorescent protein (GFP transgenic mice and immunofluorescent staining. Voluntary wheel running significantly improved water-maze cognition in the aged mice, accelerated the efficiency of glymphatic clearance, but which did not affect BBB permeability. The numbers of activated astrocytes and microglia decreased, AQP4 expression increased, and the distribution of astrocytic AQP4 was rearranged. Aβ accumulation decreased, whereas dendrites, dendritic spines and postsynaptic density protein (PSD95 increased. Our study suggests that voluntary wheel running accelerated glymphatic clearance but not BBB permeation, improved astrocytic AQP4 expression and polarization, attenuated the accumulation of amyloid plaques and neuroinflammation, and ultimately protected mice against synaptic dysfunction and a decline in spatial cognition

Wheel running exercise attenuates vulnerability to self-administer nicotine in rats.

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Sanchez, Victoria; Lycas, Matthew D; Lynch, Wendy J; Brunzell, Darlene H

2015-11-01

Preventing or postponing tobacco use initiation could greatly reduce the number of tobacco-related deaths. While evidence suggests that exercise is a promising treatment for tobacco addiction, it is not clear whether exercise could prevent initial vulnerability to tobacco use. Thus, using an animal model, we examined whether exercise attenuates vulnerability to the use and reinforcing effects of nicotine, the primary addictive chemical in tobacco. Initial vulnerability was assessed using an acquisition procedure wherein exercising (unlocked running wheel, n=10) and sedentary (locked or no wheel, n=12) male adolescent rats had access to nicotine infusions (0.01-mg/kg) during daily 21.5-h sessions beginning on postnatal day 30. Exercise/sedentary sessions (2-h/day) were conducted prior to each of the acquisition sessions. The effects of exercise on nicotine's reinforcing effects were further assessed in separate groups of exercising (unlocked wheel, n=7) and sedentary (no wheel, n=5) rats responding for nicotine under a progressive-ratio schedule with exercise/sedentary sessions (2-h/day) conducted before the daily progressive-ratio sessions. While high rates of acquisition of nicotine self-administration were observed among both groups of sedentary controls, acquisition was robustly attenuated in the exercise group with only 20% of exercising rats meeting the acquisition criterion within the 16-day testing period as compared to 67% of the sedentary controls. Exercise also decreased progressive-ratio responding for nicotine as compared to baseline and to sedentary controls. Exercise may effectively prevent the initiation of nicotine use in adolescents by reducing the reinforcing effects of nicotine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Wheel running improves REM sleep and attenuates stress-induced flattening of diurnal rhythms in F344 rats.

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Thompson, Robert S; Roller, Rachel; Greenwood, Benjamin N; Fleshner, Monika

2016-05-01

Regular physical activity produces resistance to the negative health consequences of stressor exposure. One way that exercise may confer stress resistance is by reducing the impact of stress on diurnal rhythms and sleep; disruptions of which contribute to stress-related disease including mood disorders. Given the link between diurnal rhythm disruptions and stress-related disorders and that exercise both promotes stress resistance and is a powerful non-photic biological entrainment cue, we tested if wheel running could reduce stress-induced disruptions of sleep/wake behavior and diurnal rhythms. Adult, male F344 rats with or without access to running wheels were instrumented for biotelemetric recording of diurnal rhythms of locomotor activity, heart rate, core body temperature (CBT), and sleep (i.e. REM, NREM, and WAKE) in the presence of a 12 h light/dark cycle. Following 6 weeks of sedentary or exercise conditions, rats were exposed to an acute stressor known to disrupt diurnal rhythms and produce behaviors associated with mood disorders. Prior to stressor exposure, exercise rats had higher CBT, more locomotor activity during the dark cycle, and greater %REM during the light cycle relative to sedentary rats. NREM and REM sleep were consolidated immediately following peak running to a greater extent in exercise, compared to sedentary rats. In response to stressor exposure, exercise rats expressed higher stress-induced hyperthermia than sedentary rats. Stressor exposure disrupted diurnal rhythms in sedentary rats; and wheel running reduced these effects. Improvements in sleep and reduced diurnal rhythm disruptions following stress could contribute to the health promoting and stress protective effects of exercise.

Estrous correlated modulations of circadian and ultradian wheel-running activity rhythms in LEW/Ztm rats

OpenAIRE

Wollnik, Franziska; Turek, Fred W.

1988-01-01

Estrogen treatment alters the expression of ultradian activity rhythms in male and female LEW/Ztm rats. This finding raises the possibility that the expression of ultradian rhythms may vary on different days of the estrous cycle. To test this hypothesis, we recorded the circadian and ultradian wheel-running activity rhythms of entrained (LD 12:12) and free-running sexually mature LEW/Ztm females during their 4- or 5-day estrous cycle. The mean daily activity, the duration of activity, the cir...

Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running.

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Smethells, J R; Zlebnik, N E; Miller, D K; Will, M J; Booth, F; Carroll, M E

2016-10-01

Previous research has found that rats behaviorally screened for high (vs. low) wheel running were more vulnerable to cocaine abuse. To assess the extent to which a genetic component is involved in this drug-abuse vulnerability, rats selectively bred for high or low voluntary running (HVR or LVR, respectively) were examined for differences in cocaine seeking in the present study. Female rats were trained to lever press for food and then were assessed for differences in acquisition of cocaine (0.4mg/kg; i.v.) self-administration across 10 sessions. Once acquired, rats self-administered cocaine for a 14-day maintenance phase, followed by a 14-day extinction phase when cocaine was no longer available. Subsequently, reinstatement of cocaine seeking was examined with priming injections of cocaine (5, 10 & 15mg/kg), caffeine (30mg/kg), yohimbine (2.5mg/kg) and cocaine-paired cues. A greater percentage of LVR rats met the acquisition criteria for cocaine self-administration and in fewer sessions than HVR rats. No differences in responding for cocaine were observed between phenotypes during maintenance. However, during extinction LVR rats initially responded at higher rates and persisted in cocaine seeking for a greater number of sessions. No phenotype differences were observed following drug and cue-primed reinstatement of cocaine seeking. In general, LVR rats were more sensitive to the reinforcing effects of cocaine than HVR rats during periods of transition into and out of cocaine self-administration. Thus, LVR rats sometimes showed a greater vulnerability cocaine seeking than HVR rats. Published by Elsevier Ireland Ltd.

Chronic ethanol intake alters circadian phase shifting and free-running period in mice.

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Seggio, Joseph A; Fixaris, Michael C; Reed, Jeffrey D; Logan, Ryan W; Rosenwasser, Alan M

2009-08-01

Chronic alcohol intake is associated with widespread disruptions in sleep and circadian rhythms in both human alcoholics and in experimental animals. Recent studies have demonstrated that chronic and acute ethanol treatments alter fundamental properties of the circadian pacemaker--including free-running period and responsiveness to photic and nonphotic phase-shifting stimuli--in rats and hamsters. In the present work, the authors extend these observations to the C57BL/6J mouse, an inbred strain characterized by very high levels of voluntary ethanol intake and by reliable and stable free-running circadian activity rhythms. Mice were housed individually in running-wheel cages under conditions of either voluntary or forced ethanol intake, whereas controls were maintained on plain water. Forced ethanol intake significantly attenuated photic phase delays (but not phase advances) and shortened free-running period in constant darkness, but voluntary ethanol intake failed to affect either of these parameters. Thus, high levels of chronic ethanol intake, beyond those normally achieved under voluntary drinking conditions, are required to alter fundamental circadian pacemaker properties in C57BL/6J mice. These observations may be related to the relative ethanol insensitivity displayed by this strain in several other phenotypic domains, including ethanol-induced sedation, ataxia, and withdrawal. Additional experiments will investigate chronobiological sensitivity to ethanol in a range of inbred strains showing diverse ethanol-related phenotypes.

Impact of high-fat diet and voluntary running on body weight and endothelial function in LDL receptor knockout mice.

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Langbein, Heike; Hofmann, Anja; Brunssen, Coy; Goettsch, Winfried; Morawietz, Henning

2015-05-01

Obesity and physical inactivity are important cardiovascular risk factors. Regular physical exercise has been shown to mediate beneficial effects in the prevention of cardiovascular diseases. However, the impact of physical exercise on endothelial function in proatherosclerotic low-density lipoprotein receptor deficient (LDLR(-/-)) mice has not been studied so far. Six-week-old male LDLR(-/-) mice were fed a standard diet or a high-fat diet (39 kcal% fat diet) for 20 weeks. The impact of high-fat diet and voluntary running on body weight and amount of white adipose tissue was monitored. Basal tone and endothelial function was investigated in aortic rings using a Mulvany myograph. LDLR(-/-) mice on high-fat diet had increased cumulative food energy intake, but also higher physical activity compared to mice on control diet. Body weight and amount of visceral and retroperitoneal white adipose tissue of LDLR(-/-) mice were significantly increased by high-fat diet and partially reduced by voluntary running. Endothelial function in aortae of LDLR(-/-) mice was impaired after 20 weeks on standard and high-fat diet and could not be improved by voluntary running. Basal tone showed a trend to be increased by high-fat diet. Voluntary running reduced body weight and amount of white adipose tissue in LDLR(-/-) mice. Endothelial dysfunction in LDLR(-/-) mice could not be improved by voluntary running. In a clinical context, physical exercise alone might not have an influence on functional parameters and LDL-C levels in patients with familial hypercholesterolemia. However, physical activity in these patients may be in general beneficial and should be performed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Voluntary exercise inhibits intestinal tumorigenesis in ApcMin/+ mice and azoxymethane/dextran sulfate sodium-treated mice

International Nuclear Information System (INIS)

Ju, Jihyeung; Nolan, Bonnie; Cheh, Michelle; Bose, Mousumi; Lin, Yong; Wagner, George C; Yang, Chung S

2008-01-01

Epidemiological studies suggest that physical activity reduces the risk of colon cancer in humans. Results from animal studies, however, are inconclusive. The present study investigated the effects of voluntary exercise on intestinal tumor formation in two different animal models, Apc Min/+ mice and azoxymethane (AOM)/dextran sulfate sodium (DSS)-treated mice. In Experiments 1 and 2, five-week old female Apc Min/+ mice were either housed in regular cages or cages equipped with a running wheel for 6 weeks (for mice maintained on the AIN93G diet; Experiment 1) or 9 weeks (for mice on a high-fat diet; Experiment 2). In Experiment 3, male CF-1 mice at 6 weeks of age were given a dose of AOM (10 mg/kg body weight, i.p.) and, 12 days later, 1.5% DSS in drinking fluid for 1 week. The mice were then maintained on a high-fat diet and housed in regular cages or cages equipped with a running wheel for 16 weeks. In the Apc Min/+ mice maintained on either the AIN93G or the high-fat diet, voluntary exercise decreased the number of small intestinal tumors. In the AOM/DSS-treated mice maintained on a high-fat diet, voluntary exercise also decreased the number of colon tumors. In Apc Min/+ mice, voluntary exercise decreased the ratio of serum insulin like growth factor (IGF)-1 to IGF binding protein (BP)-3 levels. It also decreased prostaglandin E 2 and nuclear β-catenin levels, but increased E-cadherin levels in the tumors. These results indicate hat voluntary exercise inhibited intestinal tumorigenesis in Apc Min/+ mice and AOM/DSS-treated mice, and the inhibitory effect is associated with decreased IGF-1/IGFBP-3 ratio, aberrant β-catenin signaling, and arachidonic acid metabolism

Effects of loaded voluntary wheel exercise on performance and muscle hypertrophy in young and old male C57Bl/6J mice.

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Soffe, Z; Radley-Crabb, H G; McMahon, C; Grounds, M D; Shavlakadze, T

2016-02-01

This study compared the capacity of young and old male C57Bl/6J mice to exercise with increasing resistance over 10 weeks, and its impact on muscle mass. Young mice (aged 15-25 weeks) were subjected to low (LR) and high (HR) resistance exercise, whereas only LR was used for old mice (107-117 weeks). Weekly patterns of voluntary wheel activity, food consumption and body weights were measured. Running patterns changed over time and with age, with two peaks of activity detected for young, but only one for old mice: speed and distance run was also less for old mice. The mass for six limb muscles was measured at the end of the experiment. The most pronounced increase in mass in response to exercise was for the soleus in young and old mice, and also quadriceps and gastrocnemius in young mice. Soleus and quadriceps muscles were analyzed histologically for myofiber number and size. A striking feature was the many small myofibers in response to exercise in young (but not old) soleus, whereas these were not present after exercise in young or old quadriceps. Overall, there was a striking difference in response to exercise between muscles and this was influenced by age. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

5-Aminoimidazole-4-carboxamide ribonucleotide prevents fat gain following the cessation of voluntary physical activity.

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Ruegsegger, Gregory N; Sevage, Joseph A; Childs, Thomas E; Grigsby, Kolter B; Booth, Frank W

2017-11-01

What is the central question of this study? We investigated whether 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) could prevent acute increases in body fat and changes in omental and subcutaneous adipose tissue following the sudden transition from physical activity to physical inactivity. What is the main finding and its importance? AICAR prevented fat gains following the transition from physical activity to inactivity to levels comparable to rats that remained physically active. AICAR and continuous physical activity produced depot-specific changes in cyclin A1 mRNA and protein that were associated with the prevention of fat gain. These findings suggest that targeting AMP-activated protein kinase signalling could oppose rapid adipose mass growth. The transition from physical activity to inactivity is associated with drastic increases in 'catch-up' fat that in turn foster the development of many obesity-associated maladies. We tested whether 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) treatment would prevent gains in body fat following the sudden transition from a physically active state to an inactive state by locking a voluntary running wheel. Male Wistar rats were either sedentary (SED) or given wheel access for 4 weeks, at which time rats with wheels continued running (RUN), had their wheel locked (WL) or had WL with daily AICAR injection (WL + AICAR) for 1 week. RUN and WL + AICAR prevented gains in body fat compared with SED and WL (P RUN and WL + AICAR compared with SED and WL groups (P run, and that together, continuous physical activity and AICAR could, at least initially in these conditions, exert similar inhibitory effects on adipogenesis in a depot-specific manner. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

Circadian rhythm disruption by a novel running wheel: Roles of exercise and arousal in blockade of the luteinizing hormone surge

Science.gov (United States)

Duncan, Marilyn J.; Franklin, Kathleen M.; Peng, Xiaoli; Yun, Christopher; Legan, Sandra J.

2014-01-01

Exposure of proestrous Syrian hamsters to a new room, cage, and novel running wheel blocks the luteinizing hormone (LH) surge until the next day in ~75% of hamsters (Legan et al, 2010) [1]. The studies described here tested the hypotheses that 1) exercise and/or 2) orexinergic neurotransmission mediate novel wheel blockade of the LH surge and circadian phase advances. Female hamsters were exposed to a 14L:10D photoperiod and activity rhythms were monitored with infra-red detectors. In Expt. 1, to test the effect of exercise, hamsters received jugular cannulae and on the next day, proestrus (Day 1), shortly before zeitgeber time 5 (ZT 5, 7 hours before lights-off) the hamsters were transported to the laboratory. After obtaining a blood sample at ZT 5, the hamsters were transferred to a new cage with a novel wheel that was either freely rotating (unlocked), or locked until ZT 9, and exposed to constant darkness (DD). Blood samples were collected hourly for 2 days from ZT 5–11 under red light for determination of plasma LH levels by radioimmunoassay. Running rhythms were monitored continuously for the next 10–14 days. The locked wheels were as effective as unlocked wheels in blocking LH surges (no Day 1 LH surge in 6/9 versus 8/8 hamsters, P>0.05) and phase advances in the activity rhythms did not differ between the groups (P= 0.28), suggesting that intense exercise is not essential for novel wheel blockade and phase advance of the proestrous LH surge. Expt. 2 tested whether orexin neurotransmission is essential for these effects. Hamsters were treated the same as in Expt. 1 except they were injected (i.p.) at ZT 4.5 and 5 with either the orexin 1 receptor antagonist SB334867 (15 mg/kg per injection) or vehicle (25% DMSO in 2-hydroxypropyl-beta-cyclodextrin (HCD). SB-334867 inhibited novel wheel blockade of the LH surge (surges blocked in 2/6 SB334867-injected animals versus 16/18 vehicle-injected animals, Pwheel running and circadian phase shifts, indicating that

Soy protein is beneficial but high-fat diet and voluntary running are detrimental to bone structure in mice.

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Yan, Lin; Graef, George L; Nielsen, Forrest H; Johnson, LuAnn K; Cao, Jay

2015-06-01

Physical activity and soy protein isolate (SPI) augmentation have been reported to be beneficial for bone health. We hypothesized that combining voluntary running and SPI intake would alleviate detrimental changes in bone induced by a high-fat diet. A 2 × 2 × 2 experiment was designed with diets containing 16% or 45% of energy as corn oil and 20% SPI or casein fed to sedentary or running male C57BL/6 mice for 14 weeks. Distal femurs were assessed for microstructural changes. The high-fat diet significantly decreased trabecular number (Tb.N) and bone mineral density (BMD) and increased trabecular separation (Tb.Sp). Soy protein instead of casein, regardless of fat content, in the diet significantly increased bone volume fraction, Tb.N, connectivity density, and BMD and decreased Tb.Sp. Voluntary running, regardless of fat content, significantly decreased bone volume fraction, Tb.N, connectivity density, and BMD and increased Tb.Sp. The high-fat diet significantly decreased osteocalcin and increased tartrate-resistant acid phosphatase 5b (TRAP 5b) concentrations in plasma. Plasma concentrations of osteocalcin were increased by both SPI and running. Running alleviated the increase in TRAP 5b induced by the high-fat diet. These findings demonstrate that a high-fat diet is deleterious, and SPI is beneficial to trabecular bone properties. The deleterious effect of voluntary running on trabecular structural characteristics indicates that there may be a maximal threshold of running beyond which beneficial effects cease and detrimental effects occur. Increases in plasma osteocalcin and decreases in plasma TRAP 5b in running mice suggest that a compensatory response occurs to counteract the detrimental effects of excessive running. Published by Elsevier Inc.

Voluntary Running Aids to Maintain High Body Temperature in Rats Bred for High Aerobic Capacity

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Karvinen, Sira M.; Silvennoinen, Mika; Ma, Hongqiang; Törmäkangas, Timo; Rantalainen, Timo; Rinnankoski-Tuikka, Rita; Lensu, Sanna; Koch, Lauren G.; Britton, Steven L.; Kainulainen, Heikki

2016-01-01

The production of heat, i.e., thermogenesis, is a significant component of the metabolic rate, which in turn affects weight gain and health. Thermogenesis is linked to physical activity (PA) level. However, it is not known whether intrinsic exercise capacity, aging, and long-term voluntary running affect core body temperature. Here we use rat models selectively bred to differ in maximal treadmill endurance running capacity (Low capacity runners, LCR and High capacity Runners, HCR), that as adults are divergent for aerobic exercise capacity, aging, and metabolic disease risk to study the connection between PA and body temperature. Ten high capacity runner (HCR) and ten low capacity runner (LCR) female rats were studied between 9 and 21 months of age. Rectal body temperature of HCR and LCR rats was measured before and after 1-year voluntary running/control intervention to explore the effects of aging and PA. Also, we determined whether injected glucose and spontaneous activity affect the body temperature differently between LCR and HCR rats at 9 vs. 21 months of age. HCRs had on average 1.3°C higher body temperature than LCRs (p temperature level of HCRs to similar levels with LCRs. The opportunity to run voluntarily had a significant impact on the body temperature of HCRs (p temperature at a similar level as when at younger age. Compared to LCRs, HCRs were spontaneously more active, had higher relative gastrocnemius muscle mass and higher UCP2, PGC-1α, cyt c, and OXPHOS levels in the skeletal muscle (p temperature of LCRs. However, glucose injection resulted in a lowering of the body temperature of LCRs (p temperature compared to rats born with low exercise capacity and disease risk. Voluntary running allowed HCRs to maintain high body temperature during aging, which suggests that high PA level was crucial in maintaining the high body temperature of HCRs. PMID:27504097

Exclusive Preference Develops Less Readily on Concurrent Ratio Schedules with Wheel-Running than with Sucrose Reinforcement

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Belke, Terry W.

2010-01-01

Previous research suggested that allocation of responses on concurrent schedules of wheel-running reinforcement was less sensitive to schedule differences than typically observed with more conventional reinforcers. To assess this possibility, 16 female Long Evans rats were exposed to concurrent FR FR schedules of reinforcement and the schedule…

Infusion of low dose glyceryl trinitrate has no consistent effect on burrowing behavior, running wheel activity and light sensitivity in female rats

DEFF Research Database (Denmark)

Christensen, Sarah Louise T; Petersen, Steffen; Sørensen, Dorte Bratbo

2016-01-01

. In the current paper we have studied the effect of glyceryl trinitrate infusion on three different rat behaviors. Methods: The stability of burrowing behavior, running wheel activity and light sensitivity towards repeated testing was evaluated also with respect to estrous cycle. Finally, the effect of glyceryl...... trinitrate on these behaviors in female rats was observed. Results: Burrowing behavior and running wheel activity were stable in the individual rat between experiments. The burrowing behavior was significantly affected by the stage of estrous cycle. The other assays were stable throughout the cycle. None...

Acute bouts of wheel running decrease cocaine self-administration: Influence of exercise output.

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Smith, Mark A; Fronk, Gaylen E; Zhang, Huailin; Magee, Charlotte P; Robinson, Andrea M

Exercise is associated with lower rates of drug use in human populations and decreases drug self-administration in laboratory animals. Most of the existing literature examining the link between exercise and drug use has focused on chronic, long-term exercise, and very few studies have examined the link between exercise output (i.e., amount of exercise) and drug self-administration. The purpose of this study was to examine the effects of acute bouts of exercise on cocaine self-administration, and to determine whether these effects were dependent on exercise output and the time interval between exercise and drug self-administration. Female rats were trained to run in automated running wheels, implanted with intravenous catheters, and allowed to self-administer cocaine on a fixed ratio (FR1) schedule of reinforcement. Immediately prior to each test session, subjects engaged in acute bouts of exercise in which they ran for 0, 30, or 60min at 12m/min. Acute bouts of exercise before test sessions decreased cocaine self-administration in an output-dependent manner, with the greatest reduction in cocaine intake observed in the 60-min exercise condition. Exercise did not reduce cocaine self-administration when wheel running and test sessions were separated by 12h, and exercise did not reduce responding maintained by food or responding during a saline substitution test. These data indicate that acute bouts of exercise decrease cocaine self-administration in a time- and output-dependent manner. These results also add to a growing body of literature suggesting that physical activity may be an effective component of drug abuse treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Microglial response to Alzheimer's disease is differentially modulated by voluntary wheel running and enriched environments.

Science.gov (United States)

Rodríguez, J J; Noristani, H N; Verkhratsky, A

2015-03-01

Alzheimer's disease (AD) is an untreatable neurodegenerative disease that deteriorates memory. Increased physical/cognitive activity reduces dementia risk by promoting neuronal and glial response. Although few studies have investigated microglial response in wild-type rodents following exposure to physical/cognitive stimulation, environmental-induced changes of microglia response to AD have been neglected. We investigated effects of running (RUN) and enriched (ENR) environments on numerical density (N v, #/mm(3)) and morphology of microglia in a triple transgenic (3×Tg-AD) mouse model of AD that closely mimics AD pathology in humans. We used immunohistochemical approach to characterise microglial domain by measuring their overall cell surface, volume and somata volume. 3×Tg-AD mice housed in standard control (STD) environment showed significant increase in microglial N v (11.7 %) in CA1 stratum lacunosum moleculare (S.Mol) of the hippocampus at 12 months compared to non-transgenic (non-Tg) animals. Exposure to combined RUN and ENR environments prevented an increase in microglial N v in 3×Tg-AD and reduced microglial numbers to non-Tg control levels. Interestingly, 3×Tg-AD mice housed solely in ENR environment displayed significant decrease in microglial N v in CA1 subfield (9.3 % decrease), stratum oriens (11.5 % decrease) and S.Mol (7.6 % decrease) of the hippocampus compared to 3×Tg-AD mice housed in STD environment. Morphological analysis revealed microglial hypertrophy due to pronounced increase in microglia surface, volume and somata volume (61, 78 and 41 %) in 3×Tg-AD mice housed in RUN (but not in ENR) compared to STD environment. These results indicate that exposure to RUN and ENR environments have differential effects on microglial density and activation-associated changes in microglial morphology.

Circadian wheel running behavior is altered in an APP/E4 mouse model of late onset Alzheimer's disease.

Science.gov (United States)

Boggs, Katelyn N; Kakalec, Peter A; Smith, Meghann L; Howell, Stefanie N; Flinn, Jane M

2017-12-01

Circadian rhythms are altered in several diseases associated with aging, one of which is Alzheimer's disease (AD). One example of a circadian rhythm is the rest-activity cycle, which can be measured in mice by monitoring their wheel-running. The present study sought to investigate differences in light phase/dark phase activity between a mouse model of late onset AD (APP/E4) and control (C57Bl6J) mice, in both the pre-plaque and post-plaques stages of the disease. To assess activity level, 24-h wheel running behavior was monitored at six months (pre-plaque) and twelve months (post-plaque) for a period of nine days. The following measures were analyzed: counts (wheel rotations) during the dark phase, counts during the light phase, hour of activity onset, and hour of activity offset. Key findings indicate that activity onset is delayed in APP/E4 mice at six and twelve months, and activity profiles for APP/E4 and C57Bl6J mice differ during the light and dark phase in such a way that APP/E4 mice run less in the early hours of the dark phase and more in the later hours of the dark phase compared to C57Bl6J mice. These findings imply that rest-activity cycle is altered in the pre-plaque stages of AD in APP/E4 mice, as they show impairments as early as six months of age. Copyright © 2017 Elsevier Inc. All rights reserved.

Exercise attenuates the metabolic effects of dim light at night.

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Fonken, Laura K; Meléndez-Fernández, O Hecmarie; Weil, Zachary M; Nelson, Randy J

2014-01-30

Most organisms display circadian rhythms that coordinate complex physiological and behavioral processes to optimize energy acquisition, storage, and expenditure. Disruptions to the circadian system with environmental manipulations such as nighttime light exposure alter metabolic energy homeostasis. Exercise is known to strengthen circadian rhythms and to prevent weight gain. Therefore, we hypothesized providing mice a running wheel for voluntary exercise would buffer against the effects of light at night (LAN) on weight gain. Mice were maintained in either dark (LD) or dim (dLAN) nights and provided either a running wheel or a locked wheel. Mice exposed to dim, rather than dark, nights increased weight gain. Access to a functional running wheel prevented body mass gain in mice exposed to dLAN. Voluntary exercise appeared to limit weight gain independently of rescuing changes to the circadian system caused by dLAN; increases in daytime food intake induced by dLAN were not diminished by increased voluntary exercise. Furthermore, although all of the LD mice displayed a 24h rhythm in wheel running, nearly half (4 out of 9) of the dLAN mice did not display a dominant 24h rhythm in wheel running. These results indicate that voluntary exercise can prevent weight gain induced by dLAN without rescuing circadian rhythm disruptions. © 2013.

Positive effects of voluntary running on metabolic syndrome-related disorders in non-obese hereditary hypertriacylglycerolemic rats.

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Vojt ch Škop

Full Text Available While metabolic syndrome is often associated with obesity, 25% of humans suffering from it are not obese and the effect of physical activity remains unclear in such cases. Therefore, we used hereditary hypertriaclyglycerolemic (HHTg rats as a unique model for studying the effect of spontaneous physical activity [voluntary running (VR] on metabolic syndrome-related disorders, such as dyslipidemia, in non-obese subjects. Adult HHTg males were fed standard (CD or high-sucrose (HSD diets ad libitum for four weeks. Within both dietary groups, some of the rats had free access to a running wheel (CD+VR, HSD+VR, whereas the controls (CD, HSD had no possibility of extra physical activity. At the end of the four weeks, we measured the effects of VR on various metabolic syndrome-associated parameters: (i biochemical parameters, (ii the content and composition of triacylglycerols (TAG, diacylglycerols (DAG, ceramides and membrane phospholipids, and (iii substrate utilization in brown adipose tissue. In both dietary groups, VR led to various positive effects: reduced epididymal and perirenal fat depots; increased epididymal adipose tissue lipolysis; decreased amounts of serum TAG, non-esterified fatty acids and insulin; a higher insulin sensitivity index. While tissue ceramide content was not affected, decreased TAG accumulation resulted in reduced and modified liver, heart and skeletal muscle DAG. VR also had a beneficial effect on muscle membrane phospholipid composition. In addition, compared with the CD group, the CD+VR rats exhibited increased fatty acid oxidation and protein content in brown adipose tissue. Our results confirm that physical activity in a non-obese model of severe dyslipidemia has many beneficial effects and can even counteract the negative effects of sucrose consumption. Furthermore, they suggest that the mechanism by which these effects are modulated involves a combination of several positive changes in lipid metabolism.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

International Nuclear Information System (INIS)

Chen, C.C.; Chang, M.W.; Chang, C.P.; Chan, S.C.; Chang, W.Y.; Yang, C.L.; Lin, M.T.

2014-01-01

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

Directory of Open Access Journals (Sweden)

C.C. Chen

2014-10-01

Full Text Available We developed a forced non-electric-shock running wheel (FNESRW system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h. An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS, an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05 and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model.

Science.gov (United States)

Chen, C C; Chang, M W; Chang, C P; Chan, S C; Chang, W Y; Yang, C L; Lin, M T

2014-10-01

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

A forced running wheel system with a microcontroller that provides high-intensity exercise training in an animal ischemic stroke model

Energy Technology Data Exchange (ETDEWEB)

Chen, C.C. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Chang, M.W. [Department of Electrical Engineering, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chang, C.P. [Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan (China); Chan, S.C.; Chang, W.Y.; Yang, C.L. [Department of Electrical Engineering, National Cheng-Kung University, Tainan, Taiwan (China); Lin, M.T. [Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan (China)

2014-08-15

We developed a forced non-electric-shock running wheel (FNESRW) system that provides rats with high-intensity exercise training using automatic exercise training patterns that are controlled by a microcontroller. The proposed system successfully makes a breakthrough in the traditional motorized running wheel to allow rats to perform high-intensity training and to enable comparisons with the treadmill at the same exercise intensity without any electric shock. A polyvinyl chloride runway with a rough rubber surface was coated on the periphery of the wheel so as to permit automatic acceleration training, and which allowed the rats to run consistently at high speeds (30 m/min for 1 h). An animal ischemic stroke model was used to validate the proposed system. FNESRW, treadmill, control, and sham groups were studied. The FNESRW and treadmill groups underwent 3 weeks of endurance running training. After 3 weeks, the experiments of middle cerebral artery occlusion, the modified neurological severity score (mNSS), an inclined plane test, and triphenyltetrazolium chloride were performed to evaluate the effectiveness of the proposed platform. The proposed platform showed that enhancement of motor function, mNSS, and infarct volumes was significantly stronger in the FNESRW group than the control group (P<0.05) and similar to the treadmill group. The experimental data demonstrated that the proposed platform can be applied to test the benefit of exercise-preconditioning-induced neuroprotection using the animal stroke model. Additional advantages of the FNESRW system include stand-alone capability, independence of subjective human adjustment, and ease of use.

Wheel traffic effect on air-filled porosity and air permeability in a soil catena across the wheel rut

DEFF Research Database (Denmark)

Berisso, Feto Esimo; Schjønning, Per; Lamandé, Mathieu

might induce different effects on soil physical properties. The objective of this study was to investigate the impact of vehicle traffic on soil physical properties and air permeability by systematic collection of samples in a transect running from the center to the outside of the wheel rut. A field...... catena running from center of the wheel rut to un wheeled part of the field ( 0, 20, 40, 50,60 and 400 cm horizontal distance). We measured water retention and air permeability (ka) at -30, -100 and -300 hPa matric potentials. At -100 hPa, we obtained consistently lower air filled under the wheel rut......The impact of wheel traffic on soil physical properties is usually quantified by randomly collecting soil cores at specific depths below the wheeled surface. However, modeling studies as well as few measurements indicated a non-uniform stress distribution in a catena across the wheel rut, which...

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances.

Science.gov (United States)

Roberts, Michael D; Brown, Jacob D; Company, Joseph M; Oberle, Lauren P; Heese, Alexander J; Toedebusch, Ryan G; Wells, Kevin D; Cruthirds, Clayton L; Knouse, John A; Ferreira, J Andries; Childs, Thomas E; Brown, Marybeth; Booth, Frank W

2013-06-01

The purpose of the present study was to partially phenotype male and female rats from generations 8-10 (G8-G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1α mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9-G10 LVR nonrunners vs. G9-G10 HVR nonrunners (P = 0.06), body fat percentage was similar between lines. G9-G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be >1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated.

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury.

Science.gov (United States)

Griesbach, Grace S; Tio, Delia L; Vincelli, Jennifer; McArthur, David L; Taylor, Anna N

2012-05-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

The effects of voluntary running exercise coincidence with social isolation after early weaning on monoaminergic axonal development.

Science.gov (United States)

Ishikawa, J; Ishikawa, A

2013-01-29

The axonal development of serotonin (5-HT)-, noradrenaline (NA)-, or tyrosine hydroxylase (TH)-containing monoaminergic neurons is affected by rearing conditions during the juvenile period. Impaired monoaminergic axonal development is implicated in the pathophysiology of emotional and cognitive dysfunction. On the other hand, exercise may have beneficial effects on emotional and learning performance in adults. We have examined whether voluntary running exercise during social isolation after early weaning (early weaning/social isolation; EI) from postnatal day (PD) 14-28 could prevent the impaired monoaminergic axonal development associated with EI. Compared with control animals reared with their dam and siblings until PD28, the EI animals showed lower density of 5-HT and NA axons in the dorsal-medial prefrontal cortex (mPFC) and basolateral nucleus of the amygdala and of NA- and TH-containing axons in the ventral-mPFC. These adverse effects of EI were not observed in rats taking part in voluntary running (EI+R) when these animals were compared to controls. The 5-HT axon density in the ventral-mPFC was significantly higher in the EI+R rats than that in the EI rats, although both these values were significantly lower than those in the control rats. The density of monoaminergic axons in the dentate gyrus and CA3 of the hippocampus was not affected by either EI or EI+R. These results suggest that the beneficial effects of voluntary running may be because of the modulation of monoaminergic axonal morphology. Our findings will hopefully provide the basis for future research into the beneficial effects of voluntary exercise during the juvenile period on brain development and emotional and cognitive performance. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Hyperphagia, lower body temperature, and reduced running wheel activity precede development of morbid obesity in New Zealand obese mice.

Science.gov (United States)

Jürgens, Hella S; Schürmann, Annette; Kluge, Reinhart; Ortmann, Sylvia; Klaus, Susanne; Joost, Hans-Georg; Tschöp, Matthias H

2006-04-13

Among polygenic mouse models of obesity, the New Zealand obese (NZO) mouse exhibits the most severe phenotype, with fat depots exceeding 40% of total body weight at the age of 6 mo. Here we dissected the components of energy balance including feeding behavior, locomotor activity, energy expenditure, and thermogenesis compared with the related lean New Zealand black (NZB) and obese B6.V-Lep(ob)/J (ob/ob) strains (11% and 65% fat at 23 wk, respectively). NZO mice exhibited a significant hyperphagia that, when food intake was expressed per metabolic body mass, was less pronounced than that of the ob/ob strain. Compared with NZB, NZO mice exhibited increased meal frequency, meal duration, and meal size. Body temperature as determined by telemetry with implanted sensors was reduced in NZO mice, but again to a lesser extent than in the ob/ob strain. In striking contrast to ob/ob mice, NZO mice were able to maintain a constant body temperature during a 20-h cold exposure, thus exhibiting a functioning cold-induced thermogenesis. No significant differences in spontaneous home cage activity were observed among NZO, NZB, and ob/ob strains. When mice had access to voluntary running wheels, however, running activity was significantly lower in NZO than NZB mice and even lower in ob/ob mice. These data indicate that obesity in NZO mice, just as in humans, is due to a combination of hyperphagia, reduced energy expenditure, and insufficient physical activity. Because NZO mice differ strikingly from the ob/ob strain in their resistance to cold stress, we suggest that the molecular defects causing hyperphagia in NZO mice are located distal from leptin and its receptor.

Estrogen and voluntary exercise interact to attenuate stress-induced corticosterone release but not anxiety-like behaviors in female rats.

Science.gov (United States)

Jones, Alexis B; Gupton, Rebecca; Curtis, Kathleen S

2016-09-15

The beneficial effects of physical exercise to reduce anxiety and depression and to alleviate stress are increasingly supported in research studies. The role of ovarian hormones in interactions between exercise and anxiety/stress has important implications for women's health, given that women are at increased risk of developing anxiety-related disorders, particularly during and after the menopausal transition. In these experiments, we tested the hypothesis that estrogen enhances the positive impact of exercise on stress responses by investigating the combined effects of exercise and estrogen on anxiety-like behaviors and stress hormone levels in female rats after an acute stressor. Ovariectomized female rats with or without estrogen were given access to running wheels for one or three days of voluntary running immediately after or two days prior to being subjected to restraint stress. We found that voluntary running was not effective at reducing anxiety-like behaviors, whether or not rats were subjected to restraint stress. In contrast, stress-induced elevations of stress hormone levels were attenuated by exercise experience in estrogen-treated rats, but were increased in rats without estrogen. These results suggest that voluntary exercise may be more effective at reducing stress hormone levels if estrogen is present. Additionally, exercise experience, or the distance run, may be important in reducing stress. Copyright © 2016 Elsevier B.V. All rights reserved.

Voluntary wheel running selectively augments insulin-stimulated vasodilation in arterioles from white skeletal muscle of insulin-resistant rats.

Science.gov (United States)

Mikus, Catherine R; Roseguini, Bruno T; Uptergrove, Grace M; Morris, E Matthew; Rector, Randy Scott; Libla, Jessica L; Oberlin, Douglas J; Borengasser, Sarah J; Taylor, Angelina M; Ibdah, Jamal A; Laughlin, Maurice Harold; Thyfault, John P

2012-11-01

Exercise (RUN) prevents declines in insulin-mediated vasodilation, an important component of insulin-mediated glucose disposal, in rats prone to obesity and insulin resistance. Determine whether RUN (1) improves insulin-stimulated vasodilation after insulin resistance has been established, and (2) differentially affects arterioles from red and white muscle. Insulin signaling and vasoreactivity to insulin (1-1000 μIU/mL) were assessed in 2A from the Gw and Gr of SED OLETF rats at 12 and 20 weeks of age (SED12, SED20) and those undergoing RUN (RUN20) or caloric restriction (CR20; to match body weight of RUN) from 12 to 20 weeks. Glucose and insulin responses to i.p. glucose were reduced in RUN20, elevated in SED20 (p RUN20 (p RUN selectively improved insulin-mediated vasodilation in Gw 2As, in part through attenuated ET-1 sensitivity/production, an adaptation that was independent of changes in adiposity and may contribute to enhanced insulin-stimulated glucose disposal. © 2012 John Wiley & Sons Ltd.

Influence of manual therapy on functional mobility after joint injury in a rat model.

Science.gov (United States)

Ruhlen, Rachel L; Snider, Eric J; Sargentini, Neil J; Worthington, Bart D; Singh, Vineet K; Pazdernik, Vanessa K; Johnson, Jane C; Degenhardt, Brian F

2013-10-01

Animal models can be used to investigate manual therapy mechanisms, but testing manipulation in animal models is problematic because animals cannot directly report their pain. To develop a rat model of inflammatory joint injury to test the efficacy of manual therapy in reducing nociception and restoring function. The authors induced acute inflammatory joint injury in rats by injecting carrageenan into the ankle and then measured voluntary running wheel activity in treated and untreated rats. Treatments included manual therapy applied to the ankle and knee of the injured limb and several analgesic medications (eg, morphine, ketorolac, prednisone). Intra-articular injection of carrageenan to the ankle produced significant swelling (diameter of the ankle increased by 64% after injection; P=.004) and a robust reduction in voluntary running wheel activity (running distance reduced by 91% compared with controls; Pmanual therapy nor analgesic medications increased running wheel activity relative to untreated rats. Voluntary running wheel activity appears to be an appropriate functional measure to evaluate the impact of an acute inflammatory joint injury. However, efforts to treat the injury did not restore running relative to untreated rats.

Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice.

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Johannes Fuss

2010-09-01

Full Text Available Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.

Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances

Science.gov (United States)

Roberts, Michael D.; Brown, Jacob D.; Company, Joseph M.; Oberle, Lauren P.; Heese, Alexander J.; Toedebusch, Ryan G.; Wells, Kevin D.; Cruthirds, Clayton L.; Knouse, John A.; Ferreira, J. Andries; Childs, Thomas E.; Brown, Marybeth

2013-01-01

The purpose of the present study was to partially phenotype male and female rats from generations 8–10 (G8–G10) that had been selectively bred to possess low (LVR) vs. high voluntary running (HVR) behavior. Over the first 6 days with wheels, 34-day-old G8 male and female LVRs ran shorter distances (P HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1α mRNA in the plantaris and soleus muscles of LVR and HVR nonrunners, although G8 LVR rats inherently possessed less NADH-positive superficial plantaris fibers compared with G8 HVR rats. While day 28 body mass tended to be greater in both sexes of G9–G10 LVR nonrunners vs. G9–G10 HVR nonrunners (P = 0.06), body fat percentage was similar between lines. G9–G10 HVRs had fat mass loss after 6 days of running compared with their prerunning values, while LVR did not lose or gain fat mass during the 6-day voluntary running period. RNA deep sequencing efforts in the nucleus accumbens showed only eight transcripts to be >1.5-fold differentially expressed between lines in HVR and LVR nonrunners. Interestingly, HVRs presented less Oprd1 mRNA, which ties in to potential differences in dopaminergic signaling between lines. This unique animal model provides further evidence as to how exercise may be mechanistically regulated. PMID:23552494

The effect of wheel eccentricity and run-out on grinding forces, waviness, wheel wear and chatter

OpenAIRE

O'DONNELL, GARRET; MURPHY, STUART

2011-01-01

PUBLISHED The effect of grinding-wheel eccentricity on grinding forces, wheel wear and final waviness height was studied. Eccentricity was evident in force oscillations and acceleration and audio measurements. A model was developed to predict final scallop-profile shape from grinding parameters and eccentricity. Recommendations are given on detecting eccentricity and determining when eccentricity is tolerable.

Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase

Science.gov (United States)

Engelmann, Alexander J.; Aparicio, Mark B.; Kim, Airee; Sobieraj, Jeffery C.; Yuan, Clara J.; Grant, Yanabel

2013-01-01

We investigated whether prior exposure to chronic wheel running (WR) alters maladaptive patterns of excessive and escalating methamphetamine intake under extended access conditions, and intravenous methamphetamine self-administration-induced neurotoxicity. Adult rats were given access to WR or no wheel (sedentary) in their home cage for 6 weeks. A set of WR rats were injected with 5-bromo-2′-deoxyuridine (BrdU) to determine WR-induced changes in proliferation (2-h old) and survival (28-day old) of hippocampal progenitors. Another set of WR rats were withdrawn (WRw) or continued (WRc) to have access to running wheels in their home cages during self-administration days. Following self-administration [6 h/day], rats were tested on the progressive ratio (PR) schedule. Following PR, BrdU was injected to determine levels of proliferating progenitors (2-h old). WRc rats self-administered significantly less methamphetamine than sedentary rats during acquisition and escalation sessions, and demonstrated reduced motivation for methamphetamine seeking. Methamphetamine reduced daily running activity of WRc rats compared with that of pre-methamphetamine days. WRw rats self-administered significantly more methamphetamine than sedentary rats during acquisition, an effect that was not observed during escalation and PR sessions. WR-induced beneficial effects on methamphetamine self-administration were not attributable to neuroplasticity effects in the hippocampus and medial prefrontal cortex, but were attributable to WR-induced inhibition of methamphetamine-induced increases in the number of neuronal nitric oxide synthase expressing neurons and apoptosis in the nucleus accumbens shell. Our results demonstrate that WR prevents methamphetamine-induced damage to forebrain neurons to provide a beneficial effect on drug-taking behavior. Importantly, WR-induced neuroprotective effects are transient and continued WR activity is necessary to prevent compulsive methamphetamine intake

49 CFR 230.113 - Wheels and tire defects.

Science.gov (United States)

2010-10-01

... tires may not have a seam running lengthwise that is within 33/4 inches of the flange. (g) Worn flanges... 49 Transportation 4 2010-10-01 2010-10-01 false Wheels and tire defects. 230.113 Section 230.113... Tenders Wheels and Tires § 230.113 Wheels and tire defects. Steam locomotive and tender wheels or tires...

29 CFR 1910.215 - Abrasive wheel machinery.

Science.gov (United States)

2010-07-01

... be securely fastened to the spindle and the bearing surface shall run true. When more than one wheel... 29 Labor 5 2010-07-01 2010-07-01 false Abrasive wheel machinery. 1910.215 Section 1910.215 Labor... OCCUPATIONAL SAFETY AND HEALTH STANDARDS Machinery and Machine Guarding § 1910.215 Abrasive wheel machinery. (a...

Burrowing as a novel voluntary strength training method for mice: A comparison of various voluntary strength or resistance exercise methods.

Science.gov (United States)

Roemers, P; Mazzola, P N; De Deyn, P P; Bossers, W J; van Heuvelen, M J G; van der Zee, E A

2018-04-15

Voluntary strength training methods for rodents are necessary to investigate the effects of strength training on cognition and the brain. However, few voluntary methods are available. The current study tested functional and muscular effects of two novel voluntary strength training methods, burrowing (digging a substrate out of a tube) and unloaded tower climbing, in male C57Bl6 mice. To compare these two novel methods with existing exercise methods, resistance running and (non-resistance) running were included. Motor coordination, grip strength and muscle fatigue were measured at baseline, halfway through and near the end of a fourteen week exercise intervention. Endurance was measured by an incremental treadmill test after twelve weeks. Both burrowing and resistance running improved forelimb grip strength as compared to controls. Running and resistance running increased endurance in the treadmill test and improved motor skills as measured by the balance beam test. Post-mortem tissue analyses revealed that running and resistance running induced Soleus muscle hypertrophy and reduced epididymal fat mass. Tower climbing elicited no functional or muscular changes. As a voluntary strength exercise method, burrowing avoids the confounding effects of stress and positive reinforcers elicited in forced strength exercise methods. Compared to voluntary resistance running, burrowing likely reduces the contribution of aerobic exercise components. Burrowing qualifies as a suitable voluntary strength training method in mice. Furthermore, resistance running shares features of strength training and endurance (aerobic) exercise and should be considered a multi-modal aerobic-strength exercise method in mice. Copyright © 2017 Elsevier B.V. All rights reserved.

Running rescues a fear-based contextual discrimination deficit in aged mice

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Melody V. Wu

2015-08-01

Full Text Available Normal aging and exercise exert extensive, often opposing, effects on the dentate gyrus (DG of the hippocampus altering volume, synaptic function, and behaviors. The DG is especially important for behaviors requiring pattern separation—a cognitive process that enables animals to differentiate between highly similar contextual experiences. To determine how age and exercise modulate pattern separation in an aversive setting, young, aged, and aged mice provided with a running wheel were assayed on a fear-based contextual discrimination task. Aged mice showed a profound impairment in contextual discrimination compared to young animals. Voluntary exercise rescued this deficit to such an extent that behavioral pattern separation of aged-run mice was now similar to young animals. Running also resulted in a significant increase in the number of immature neurons with tertiary dendrites in aged mice. Despite this, neurogenesis levels in aged-run mice were still considerably lower than in young animals. Thus, mechanisms other than DG neurogenesis likely play significant roles in improving behavioral pattern separation elicited by exercise in aged animals.

49 CFR 229.75 - Wheels and tire defects.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Wheels and tire defects. 229.75 Section 229.75....75 Wheels and tire defects. Wheels and tires may not have any of the following conditions: (a) A... two adjoining spots that are each two or more inches in length. (e) A seam running lengthwise that is...

Influence of Physical Exercise and Food Restriction on the Biomechanical Properties of the Femur of Ageing Male Rats

DEFF Research Database (Denmark)

Thomsen, Jesper Skovhus; Skalicky, Monika; Viidik, Andrus

2008-01-01

BACKGROUND: Voluntary running in wheels as well as food reduction increase the life spans of rats. Disparate parameters such as the collagen biomarker of ageing and the development of kidney pathologies are decreased by voluntary exercise. There are few reports on the influence of physical exercise...... were used: baseline (BL), voluntarily running in wheels (RW), food restriction to attain pair weight with RW animals (PW), forced running in treadmills (TM), and sedentary controls (SE). The biomechanical properties of femoral neck, diaphysis, and distal metaphysis were measured. RESULTS: While...

Computation of wheel-rail contact force for non-mapping wheel-rail profile of Translohr tram

Science.gov (United States)

Ji, Yuanjin; Ren, Lihui; Zhou, Jinsong

2017-09-01

Translohr tram has steel wheels, in V-like arrangements, as guide wheels. These operate over the guide rails in inverted-V arrangements. However, the horizontal and vertical coordinates of the guide wheels and guide rails are not always mapped one-to-one. In this study, a simplified elastic method is proposed in order to calculate the contact points between the wheels and the rails. By transforming the coordinates, the non-mapping geometric relationship between wheel and rail is converted into a mapping relationship. Considering the Translohr tram's multi-point contact between the guide wheel and the guide rail, the elastic-contact hypothesis take into account the existence of contact patches between the bodies, and the location of the contact points is calculated using a simplified elastic method. In order to speed up the calculation, a multi-dimensional contact table is generated, enabling the use of simulation for Translohr tram running on curvatures with different radii.

Early motor deficits in mouse disease models are reliably uncovered using an automated home-cage wheel-running system: a cross-laboratory validation.

Science.gov (United States)

Mandillo, Silvia; Heise, Ines; Garbugino, Luciana; Tocchini-Valentini, Glauco P; Giuliani, Alessandro; Wells, Sara; Nolan, Patrick M

2014-03-01

Deficits in motor function are debilitating features in disorders affecting neurological, neuromuscular and musculoskeletal systems. Although these disorders can vary greatly with respect to age of onset, symptomatic presentation, rate of progression and severity, the study of these disease models in mice is confined to the use of a small number of tests, most commonly the rotarod test. To expand the repertoire of meaningful motor function tests in mice, we tested, optimised and validated an automated home-cage-based running-wheel system, incorporating a conventional wheel with evenly spaced rungs and a complex wheel with particular rungs absent. The system enables automated assessment of motor function without handler interference, which is desirable in longitudinal studies involving continuous monitoring of motor performance. In baseline studies at two test centres, consistently significant differences in performance on both wheels were detectable among four commonly used inbred strains. As further validation, we studied performance in mutant models of progressive neurodegenerative diseases--Huntington's disease [TgN(HD82Gln)81Dbo; referred to as HD mice] and amyotrophic lateral sclerosis [Tg(SOD1G93A)(dl)1/GurJ; referred to as SOD1 mice]--and in a mutant strain with subtle gait abnormalities, C-Snap25(Bdr)/H (Blind-drunk, Bdr). In both models of progressive disease, as with the third mutant, we could reliably and consistently detect specific motor function deficits at ages far earlier than any previously recorded symptoms in vivo: 7-8 weeks for the HD mice and 12 weeks for the SOD1 mice. We also conducted longitudinal analysis of rotarod and grip strength performance, for which deficits were still not detectable at 12 weeks and 23 weeks, respectively. Several new parameters of motor behaviour were uncovered using principal component analysis, indicating that the wheel-running assay could record features of motor function that are independent of rotarod

Voluntary Running Depreciates the Requirement of Ca[superscript 2+]-Stimulated cAMP Signaling in Synaptic Potentiation and Memory Formation

Science.gov (United States)

Zheng, Fei; Zhang, Ming; Ding, Qi; Sethna, Ferzin; Yan, Lily; Moon, Changjong; Yang, Miyoung; Wang, Hongbing

2016-01-01

Mental health and cognitive functions are influenced by both genetic and environmental factors. Although having active lifestyle with physical exercise improves learning and memory, how it interacts with the specific key molecular regulators of synaptic plasticity is largely unknown. Here, we examined the effects of voluntary running on long-term…

Rats do not respond differently in the presence of stimuli signaling wheel-running reinforcers of different durations.

Science.gov (United States)

Belke, Terry W

2007-05-01

Rats were exposed to a fixed interval 30 s schedule that produced opportunities to run of equal or unequal durations to assess the effect of differences in duration on responding. Each duration was signaled by a different stimulus. Wheel-running reinforcer duration pairs were 30 s 30 s, 50 s 10 s, and 55 s 5 s. An analysis of median postreinforcement pause duration and mean local lever-pressing rates broken down by previous reinforcer duration and duration of signaled upcoming reinforcer showed that postreinforcement pause duration was affected by the duration of the previous reinforcer but not by the stimulus signaling the duration of the upcoming reinforcer. Local lever-pressing rates were not affected by either previous or upcoming reinforcer duration. In general, the results are consistent with indifference between these durations obtained using a concurrent choice procedure.

Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

Science.gov (United States)

Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

2015-09-01

In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity. Copyright © 2015 Elsevier Inc. All rights reserved.

Voluntary exercise decreases atherosclerosis in nephrectomised ApoE knockout mice.

Directory of Open Access Journals (Sweden)

Cecilia M Shing

Full Text Available Cardiovascular disease is the main cause of morbidity and mortality in patients with kidney disease. The effectiveness of exercise for cardiovascular disease that is accelerated by the presence of chronic kidney disease remains unknown. The present study utilized apolipoprotein E knockout mice with 5/6 nephrectomy as a model of combined kidney disease and cardiovascular disease to investigate the effect of exercise on aortic plaque formation, vascular function and systemic inflammation. Animals were randomly assigned to nephrectomy or control and then to either voluntary wheel running exercise or sedentary. Following 12-weeks, aortic plaque area was significantly (p0.05. Nephrectomy increased IL-6 and TNF-α concentrations compared with control mice (p0.05. Exercise was an effective non-pharmacologic approach to slow cardiovascular disease in the presence of kidney disease in the apolipoprotein E knockout mouse.

Early motor deficits in mouse disease models are reliably uncovered using an automated home-cage wheel-running system: a cross-laboratory validation

Science.gov (United States)

Mandillo, Silvia; Heise, Ines; Garbugino, Luciana; Tocchini-Valentini, Glauco P.; Giuliani, Alessandro; Wells, Sara; Nolan, Patrick M.

2014-01-01

Deficits in motor function are debilitating features in disorders affecting neurological, neuromuscular and musculoskeletal systems. Although these disorders can vary greatly with respect to age of onset, symptomatic presentation, rate of progression and severity, the study of these disease models in mice is confined to the use of a small number of tests, most commonly the rotarod test. To expand the repertoire of meaningful motor function tests in mice, we tested, optimised and validated an automated home-cage-based running-wheel system, incorporating a conventional wheel with evenly spaced rungs and a complex wheel with particular rungs absent. The system enables automated assessment of motor function without handler interference, which is desirable in longitudinal studies involving continuous monitoring of motor performance. In baseline studies at two test centres, consistently significant differences in performance on both wheels were detectable among four commonly used inbred strains. As further validation, we studied performance in mutant models of progressive neurodegenerative diseases – Huntington’s disease [TgN(HD82Gln)81Dbo; referred to as HD mice] and amyotrophic lateral sclerosis [Tg(SOD1G93A)dl1/GurJ; referred to as SOD1 mice] – and in a mutant strain with subtle gait abnormalities, C-Snap25Bdr/H (Blind-drunk, Bdr). In both models of progressive disease, as with the third mutant, we could reliably and consistently detect specific motor function deficits at ages far earlier than any previously recorded symptoms in vivo: 7–8 weeks for the HD mice and 12 weeks for the SOD1 mice. We also conducted longitudinal analysis of rotarod and grip strength performance, for which deficits were still not detectable at 12 weeks and 23 weeks, respectively. Several new parameters of motor behaviour were uncovered using principal component analysis, indicating that the wheel-running assay could record features of motor function that are independent of rotarod

Voluntary running of defined distances reduces body adiposity and its associated inflammation in C57BL/6 mice fed a high-fat diet.

Science.gov (United States)

Yan, Lin; Sundaram, Sneha; Nielsen, Forrest H

2017-11-01

This study investigated the effect of voluntary running of defined distances on body adiposity in male C57BL/6 mice fed a high-fat diet. Mice were assigned to 6 groups and fed a standard AIN93G diet (sedentary) or a modified high-fat AIN93G diet (sedentary; unrestricted running; or 75%, 50%, or 25% of unrestricted running) for 12 weeks. The average running distance was 8.3, 6.3, 4.2, and 2.1 km/day for the unrestricted, 75%, 50%, and 25% of unrestricted runners, respectively. Body adiposity was 46% higher in sedentary mice when fed the high-fat diet instead of the standard diet. Running decreased adiposity in mice fed the high-fat diet in a dose-dependent manner but with no significant difference between sedentary mice and those running 2.1 km/day. In sedentary mice, the high-fat instead of the standard diet increased insulin resistance, hepatic triacylglycerides, and adipose and plasma concentrations of leptin and monocyte chemotactic protein-1 (MCP-1). Running reduced these variables in a dose-dependent manner. Adipose adiponectin was lowest in sedentary mice fed the high-fat diet; running raised adiponectin in both adipose tissue and plasma. Running 8.3 and 6.3 km/day had the greatest, but similar, effects on the aforementioned variables. Running 2.1 km/day did not affect these variables except, when compared with sedentariness, it significantly decreased MCP-1. The findings showed that running 6.3 kg/day was optimal for reducing adiposity and associated inflammation that was increased in mice by feeding a high-fat diet. The findings suggest that voluntary running of defined distances may counteract the obesogenic effects of a high-fat diet.

Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running

Directory of Open Access Journals (Sweden)

Azhar Salman

2010-04-01

Full Text Available Abstract Background The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid metabolism. Methods Two groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P P P P Conclusion These data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity and lowering of circulating FFA levels.

Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

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Jonathan eShelton

2015-01-01

Full Text Available Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6 induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg. Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15 or advance (CT22 wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light-induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals.

Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum.

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Peter J Clark

Full Text Available Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress. Impaired escape behavior is a result of stress-sensitized serotonin (5-HT neuron activity in the dorsal raphe (DRN and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS and lateral (DLS dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress.

Disincentives to voluntary transactions

International Nuclear Information System (INIS)

Anon.

1991-01-01

Current legal, regulatory and institutional standards and practices provide several disincentives for a utility wishing to engage in voluntary wheeling transactions, and are discussed here. These disincentives largely arise from the fact that regulation, like the transmission system itself, is based on the notion of integrated utilities engaging in transactions largely for reliability reasons. Factors which fall into this category are: a pricing regime based on embedded costs, the ratemaking treatment of revenues derived from coordination and transmission services, and several provisions in legislation and FERC regulations

Assessment of a rail vehicle running with the damaged wheel on a ride comfort for passengers

Directory of Open Access Journals (Sweden)

Dižo Ján

2018-01-01

Full Text Available In certain conditions rail vehicles wheels can be during operation damaged. Then, the profile of wheels is no longer circular, but it is changed depending on the type and severity of defects. When such rail vehicle with the damaged wheel operates, the quality of a ride comfort for passenger is degraded. This article is focused on the assessment of ride comfort for passenger based on results obtained from dynamic analyses. Simulations and calculations were carried out in commercial multibody software. In our research we considered one type of the railway wheel untrueness – wheel-flat. This type of wheel damaging is relatively common and has such influence on the ride comfort for passenger worsening, which needs to be detected and investigated.

Cardioprotective Effects of Voluntary Exercise in a Rat Model: Role of Matrix Metalloproteinase-2

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Anikó Pósa

2015-01-01

Full Text Available Background. Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury. Methods. Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine, AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured. Results. Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa and the coronary effluent (64 kDa MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size. Conclusion. 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2.

Sensor set-up for wireless measurement of automotive rim and wheel parameters in laboratory conditions

Science.gov (United States)

Borecki, M.; Prus, P.; Korwin-Pawlowski, M. L.; Rychlik, A.; Kozubel, W.

2017-08-01

Modern rims and wheels are tested at the design and production stages. Tests can be performed in laboratory conditions and on the ride. In the laboratory, complex and costly equipment is used, as for example wheel balancers and impact testers. Modern wheel balancers are equipped with electronic and electro-mechanical units that enable touch-less measurement of dimensions, including precision measurement of radial and lateral wheel run-out, automatic positioning and application of the counterweights, and vehicle wheel set monitoring - tread wear, drift angles and run-out unbalance. Those tests are performed by on-wheel axis measurements with laser distance meters. The impact tester enables dropping of weights from a defined height onto a wheel. Test criteria are the loss of pressure of the tire and generation of cracks in the wheel without direct impact of the falling weights. In the present paper, a set up composed of three accelerometers, a temperature sensor and a pressure sensor is examined as the base of a wheel tester. The sensor set-up configuration, on-line diagnostic and signal transmission are discussed.

Using the Activity-based Anorexia Rodent Model to Study the Neurobiological Basis of Anorexia Nervosa.

Science.gov (United States)

Chowdhury, Tara Gunkali; Chen, Yi-Wen; Aoki, Chiye

2015-10-22

Anorexia nervosa (AN) is a psychiatric illness characterized by excessively restricted caloric intake and abnormally high levels of physical activity. A challenging illness to treat, due to the lack of understanding of the underlying neurobiology, AN has the highest mortality rate among psychiatric illnesses. To address this need, neuroscientists are using an animal model to study how neural circuits may contribute toward vulnerability to AN and may be affected by AN. Activity-based anorexia (ABA) is a bio-behavioral phenomenon described in rodents that models the key symptoms of anorexia nervosa. When rodents with free access to voluntary exercise on a running wheel experience food restriction, they become hyperactive - running more than animals with free access to food. Here, we describe the procedures by which ABA is induced in adolescent female C57BL/6 mice. On postnatal day 36 (P36), the animal is housed with access to voluntary exercise on a running wheel. After 4 days of acclimation to the running wheel, on P40, all food is removed from the cage. For the next 3 days, food is returned to the cage (allowing animals free food access) for 2 hr daily. After the fourth day of food restriction, free access to food is returned and the running wheel is removed from the cage to allow the animals to recover. Continuous multi-day analysis of running wheel activity shows that mice become hyperactive within 24 hr following the onset of food restriction. The mice run even during the limited time during which they have access to food. Additionally, the circadian pattern of wheel running becomes disrupted by the experience of food restriction. We have been able to correlate neurobiological changes with various aspects of the animals' wheel running behavior to implicate particular brain regions and neurochemical changes with resilience and vulnerability to food-restriction induced hyperactivity.

Peculiarities of Clutch Forming Rails and Wheel Block Construction

Science.gov (United States)

Shiler, V. V.; Galiev, I. I.; Shiler, A. V.

2018-03-01

The clutch of the wheel and rail is significantly influenced by the design features of the standard wheel pair, which are manifested in the presence of "parasitic" slipping of the wheels along the rails during its movement. The purpose of the presented work is to evaluate new design solutions for wheel sets. The research was carried out using methods of comparative simulation modelling and physical prototyping. A new design of the wheel pair (block wheel pair) is proposed, which features an independent rotation of all surfaces of the wheels in contact with the rails. The block construction of the wheel pair forms open mechanical contours with the track gauge, which completely eliminates the "parasitic" slippage. As a result, in the process of implementing traction or braking forces, the coupling coefficient of the block construction of the wheel pair is significantly higher than that of existing structures. In addition, in the run-out mode, the resistance to movement of the block wheel pair is half as much. All this will allow one to significantly reduce the energy consumption for traction of trains, wear of track elements and crew, and to increase the speed and safety of train traffic.

Analyzing the Wheeled Vehicle Gearbox Structures for Running in Harsh Conditions

Directory of Open Access Journals (Sweden)

V. V. Vasiliev

2015-01-01

Full Text Available In domestic automotive industry the need for transition from transmission with manual control to automatic gearboxes (GB emerged long ago. Regarding the leading foreign manufacturers (Allison, ZF, Eaton, etc., an experience in design of automatic transmissions and the level of technological development is incomparably small. Thus, to have an informed choice of the gearbox structure types and control system is a relevant problem. Application efficiency of this or other gearbox depends both on its adaptability to the actual operating conditions and on the quality of transition refinement. This paper analyzes the special features of the gear change process in the most common types of automatic gearboxes. Constructive feasibilities of an "ideal" gear change (without power loss and strategies for gear shifting are compared. The paper offers an overview of common problems when achieving these goals and the ways to solve them. An automatic transmission of the particular type used in the wheeled vehicles under off-road conditions determines the probability of maintaining their mobility. This is due to the phenomenon of wheel`s breakdown to slipping caused by sharp increase of torque on the wheel. Planetary hydromechanical transmissions (AT provide continuous input torque to the wheels, but they are expensive and difficult to manufacture and use. Besides, to provide a high number of density ratios in them is more complicated than in the automated and manual transmissions (AMT. This is important when moving long in the lower gears under difficult conditions. Compared with AT dual clutch transmissions due to design features require even more precise and fast control system of actuators and engine. Automation of constant-mesh or synchromesh transmissions provides a significant reduction in the duration of interruption in torque delivery. If it is not enough to increase mobility in the harsh conditions, a rational choice is to use a transmission type of TCCT

Thermoregulatory responses to acute heat loads in rats following spontaneous running.

Science.gov (United States)

Sugimoto, N; Shido, O; Sakurada, S; Nagasaka, T

1999-02-01

Earlier studies showed that spontaneous exercise training in rodents shifted their core temperature and thermoeffector thresholds to high levels. The present study investigated heat loss and heat production responses to acute heat loads of exercise-trained rats. The exercise-trained rats were allowed to run in a running wheel freely for 6 months, while the sedentary controls were denied access to the wheel during the same period. Then, they were loosely restrained and put in a direct calorimeter. After thermal equilibrium had been attained, they were warmed for 30 min with an intraperitoneal electric heater (internal heating). At least 2 h later, the rats were externally warmed for 90 min by raising the ambient temperature from 24 to 38C (external warming). Hypothalamic temperature (Thy), evaporative and nonevaporative heat loss (R+C+K) and heat production were measured. Internal and external heating significantly increased Thy. During internal heating, the magnitude of the increase in Thy was significantly smaller and the amount of increase in (R+C+K) was significantly greater in the exercise-trained rats than in the controls. The slope showing the relationship between Thy and (R+C+K) in the trained rats was significantly steeper than that in the controls. During external warming, the magnitude of increase in Thy of the exercise-trained rats was significantly greater than that of the controls. The slope showing the relationship between Thy and (R+C+K) in the trained rats was not different from that in the controls. Changes in evaporative heat loss and heat production during the two types of heat load did not differ between the two groups. The results suggest that, in rats, exercise training with voluntary running improves heat tolerance through enhancing nonevaporative heat loss response. However, this may be the case only when the rats are subjected to a direct internal heat load.

Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

Science.gov (United States)

Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

2015-11-01

It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

Simulation and Measurement of Wheel on Rail Fatigue and Wear

OpenAIRE

Dirks, Babette

2015-01-01

The life of railway wheels and rails has been decreasing in recent years. This is mainly caused by more traffic and running at higher vehicle speed. A higher speed usually generates higher forces, unless compensated by improved track and vehicle designs, in the wheel-rail contact, resulting in more wear and rolling contact fatigue (RCF) damage to the wheels and rails. As recently as 15 years ago, RCF was not recognised as a serious problem. Nowadays it is a serious problem in many countries a...

Energy loss optimization of run-off-road wheels applying imperialist competitive algorithm

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Hamid Taghavifar

2014-08-01

Full Text Available The novel imperialist competitive algorithm (ICA has presented outstanding fitness on various optimization problems. Application of meta-heuristics has been a dynamic studying interest of the reliability optimization to determine idleness and reliability constituents. The application of a meta-heuristic evolutionary optimization method, imperialist competitive algorithm (ICA, for minimization of energy loss due to wheel rolling resistance in a soil bin facility equipped with single-wheel tester is discussed. The required data were collected thorough various designed experiments in the controlled soil bin environment. Local and global searching of the search space proposed that the energy loss could be reduced to the minimum amount of 15.46 J at the optimized input variable configuration of wheel load at 1.2 kN, tire inflation pressure of 296 kPa and velocity of 2 m/s. Meanwhile, genetic algorithm (GA, particle swarm optimization (PSO and hybridized GA–PSO approaches were benchmarked among the broad spectrum of meta-heuristics to find the outperforming approach. It was deduced that, on account of the obtained results, ICA can achieve optimum configuration with superior accuracy in less required computational time.

Autologous Minced Muscle Grafts: A Tissue Engineering Therapy for the Volumetric Loss of Skeletal Muscle

Science.gov (United States)

2013-07-24

in nonrepaired muscles was restored). Additionally, voluntary wheel running was shown to reduce the heightened accu- mulation of extracellular matrix...is apparent in a variety of animal injury models, such as toxin (44), freeze (67), eccentric contraction (34), laceration (31), and ischemia-rep...were given access to running wheels in their cages beginning at 1 wk postinjury and until 2 or 8 wk postinjury, at which time muscle mechanical

Experiments on a Tail-wheel Shimmy

Science.gov (United States)

Harling, R; Dietz, O

1954-01-01

Model tests on the "running belt" and tests with a full-scale tail wheel were made on a rotating drum as well as on a runway in order to investigate the causes of the undesirable shimmy phenomena frequently occurring on airplane tail wheels, and the means of avoiding them. The small model (scale 1:10) permitted simulation of the mass, moments of inertia, and fuselage stiffness of the airplane and determination of their influence on the shimmy, whereas by means of the larger model with pneumatic tires (scale 1:2) more accurate investigations were made on the tail wheel itself. The results of drum and road tests show good agreement with one another and with model values. Detailed investigations were made regarding the dependence of the shimmy tendency on trail, rolling speed, load, size of tires, ground friction,and inclination of the swivel axis; furthermore, regarding the influence of devices with restoring effect on the tail wheel, and the friction damping required for prevention of shimmy. Finally observations from slow-motion pictures are reported and conclusions drawn concerning the influence of tire deformation.

Problems of locomotive wheel wear in fleet replacement

Directory of Open Access Journals (Sweden)

L.P. Lingaytis

2013-08-01

Full Text Available Purpose. To conduct a research and find out the causes of defects appearing on the wheel thread of freight locomotives 2М62 and SIEMENS ER20CF. Methodology. To find the ways to solve this problem comparing the locomotive designs and their operating conditions. Findings. After examining the nature of the wheel wear the main difference was found: in locomotives of the 2M62 line wears the wheel flange, and in the locomotives SIEMENS ER20CF – the tread surface. After installation on the 2M62 locomotive the lubrication system of flanges their wear rate significantly decreased. On the new freight locomotives SIEMENS ER20CF the flange lubrication systems of the wheel set have been already installed at the factory, however the wheel thread is wearing. As for locomotives 2M62, and on locomotives SIEMENS ER20CF most wear profile skating wheels of the first wheel set. On both locomotive lines the 2М62 and the SIEMENS ER20CF the tread profile of the first wheel set most of all is subject to the wear. After reaching the 170 000 km run, the tread surface of some wheels begins to crumble. There was a suspicion that the reason for crumb formation of the wheel surface may be insufficient or excessive wheel hardness or its chemical composition. In order to confirm or deny this suspicion the following studies were conducted: the examination of the rim surface, the study of the wheel metal hardness and the document analysis of the wheel production and their comparison with the results of wheel hardness measurement. Practical value. The technical condition of locomotives is one of the bases of safety and reliability of the rolling stock. The reduction of the wheel wear significantly reduces the operating costs of railway transport. After study completion it was found that there was no evidence to suggest that the ratio of the wheel-rail hardness could be the cause of the wheel surface crumbling.

Strain screen and haplotype association mapping of wheel running in inbred mouse strains.

Science.gov (United States)

Lightfoot, J Timothy; Leamy, Larry; Pomp, Daniel; Turner, Michael J; Fodor, Anthony A; Knab, Amy; Bowen, Robert S; Ferguson, David; Moore-Harrison, Trudy; Hamilton, Alicia

2010-09-01

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (approximately 8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

Complex eigenvalue analysis of railway wheel/rail squeal

African Journals Online (AJOL)

DR OKE

Squeal noise from wheel/rail and brake disc/pad frictional contact is typical in railways. ... squeal noise by multibody simulation of a rail car running on rigid rails. ... system, traditional complex eigenvalue analysis by finite element was used.

Wheel slip dump valve for railway braking system

Science.gov (United States)

Zhang, Xuan; Zhang, LiHao; Li, QingXuan; Shi, YanTao

2017-09-01

As we all know, pneumatic braking system plays an important role in the safety of the whole vehicle. In the anti slip braking system, the pressure of braking cylinder can be adjusted by the quick power response of wheel slip dump valve, so that the lock situation won’t occur during vehicle service. During the braking of railway vehicles, the braking force provided by braking disc reduces vehicle’s speed. But the locking slip will happen due to the oversize of braking force or the reduction of sticking coefficient between wheel and rail. It will cause not only the decline of braking performance but also the increase of braking distance. In the meanwhile, it will scratch the wheel and influence the stable running of vehicles. Now, the speed of passenger vehicle has been increased. In order to shorten the braking distance as far as possible, sticking stickiness must be fully applied. So the occurrence probability of wheel slip is increased.

Experimental analysis and regression prediction of desiccant wheel behavior in high temperature heat pump and desiccant wheel air-conditioning system

DEFF Research Database (Denmark)

Sheng, Ying; Zhang, Yufeng; Sun, Yuexia

2014-01-01

The objectives of this study are to evaluate the performance of desiccant wheel (DW) in the running system and obtain the useful data for practical application. The combined influences of multiple variables on the performance of desiccant wheel are investigated based on evaluating the indexes...... of moisture removal capacity, dehumidification effectiveness, dehumidification coefficient of performance and sensible energy ratio. The results show that higher effect on the dehumidification is due to the regeneration temperature and outdoor air humidity ratio rather than the outdoor air temperature...... and the ratio between regeneration and process air flow rates. A simple method based on multiple linear regression theory for predicting the performance of the wheel has been proposed. The predicted values and the experimental data are compared and good agreements are obtained. Regression models are established...

Effects of Running Wheel Activity and Dietary HMB and β-alanine Co-Supplementation on Muscle Quality in Aged Male Rats.

Science.gov (United States)

Russ, D W; Acksel, C; McCorkle, K W; Edens, N K; Garvey, S M

2017-01-01

Loss of skeletal muscle function is linked to increased risk for loss of health and independence in older adults. Dietary interventions that can enhance aging muscle function, alone or in combination with exercise, may offer an effective way to reduce these risks. The goal of this study was to evaluate the muscular effects of beta-hydroxy-beta-methylbutyrate (HMB) and beta-alanine (β-Ala) co-supplementation in aged Sprague-Dawley rats with voluntary access to running wheels (RW). Aged (20 months) rats were housed with ad libitum access to RW while on a purified diet for 4 weeks, then balanced for RW activity and assigned to either a control or an experimental diet (control + HMB and β-Ala) for the next 4 weeks (n = 10/group). At the end of the study, we assessed muscle size, in situ force and fatigability in the medial gastrocnemius muscles, as well as an array of protein markers related to various age- and activity-responsive signaling pathways. Dietary HMB+β-Ala did not improve muscle force or fatigue resistance, but a trend for increased muscle cross-sectional area (CSA) was observed (P = 0.077). As a result, rats on the experimental diet exhibited reduced muscle quality (force/CSA; P = 0.032). Dietary HMB+β-Ala reduced both the abundance of PGC1-α (P = 0.050) and the ratio of the lipidated to non-lipidated forms of microtubule-associated protein 1 light chain 3 beta (P = 0.004), markers of mitochondrial biogenesis and autophagy, respectively. Some alterations in myostatin signaling also occurred in the dietary HMB+β-Ala group. There was an unexpected difference (P = 0.046) in RW activity, which increased throughout the study in the animals on the control diet, but not in animals on the experimental diet. These data suggest that the short-term addition of dietary HMB+β-Ala to modest physical activity provided little enhancement of muscle function in this model of uncomplicated aging.

Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice.

Science.gov (United States)

Nakajima, Sanae; Ohsawa, Ikuroh; Ohta, Shigeo; Ohno, Makoto; Mikami, Toshio

2010-08-25

Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise-induced enhancement of IGF-1 protein and GST activity in the brain. Copyright 2010 Elsevier B.V. All rights reserved.

Environmental enrichment in the absence of wheel running produces beneficial behavioural and anti-oxidative effects in rats.

Science.gov (United States)

Mármol, F; Sánchez, J; Torres, M N; Chamizo, V D

2017-11-01

The effects of early environmental enrichment (EE) when solving a simple spatial task in adult male rats were assessed. After weaning, rats were housed in pairs in enriched or standard cages (EE and control groups) for two and a half months. Then the rats were trained in a triangular-shaped pool to find a hidden platform whose location was defined in terms of two sources of information, a landmark outside the pool and a particular corner of the pool. As expected, enriched rats reached the platform faster than control animals. Enriched rats also performed better on a subsequent test trial without the platform with the geometry cue individually presented (in the absence of the landmark). Most importantly, the beneficial effects of the present protocol were obtained in the absence of wheel running. Additionally, the antioxidative effects in the hippocampus produced by the previous protocol are also shown. Copyright © 2017 Elsevier B.V. All rights reserved.

Voluntary Physical Exercise Improves Subsequent Motor and Cognitive Impairments in a Rat Model of Parkinson’s Disease

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Shih-Chang Hsueh

2018-02-01

Full Text Available Background: Parkinson’s disease (PD is typically characterized by impairment of motor function. Gait disturbances similar to those observed in patients with PD can be observed in animals after injection of neurotoxin 6-hydroxydopamine (6-OHDA to induce unilateral nigrostriatal dopamine depletion. Exercise has been shown to be a promising non-pharmacological approach to reduce the risk of neurodegenerative disease. Methods: In this study, we investigated the long-term effects of voluntary running wheel exercise on gait phenotypes, depression, cognitive, rotational behaviors as well as histology in a 6-OHDA-lesioned rat model of PD. Results: We observed that, when compared with the non-exercise controls, five-week voluntary exercise alleviated and postponed the 6-OHDA-induced gait deficits, including a significantly improved walking speed, step/stride length, base of support and print length. In addition, we found that the non-motor functions, such as novel object recognition and forced swim test, were also ameliorated by voluntary exercise. However, the rotational behavior of the exercise group did not show significant differences when compared with the non-exercise group. Conclusions: We first analyzed the detailed spatiotemporal changes of gait pattern to investigate the potential benefits after long-term exercise in the rat model of PD, which could be useful for future objective assessment of locomotor function in PD or other neurological animal models. Furthermore, these results suggest that short-term voluntary exercise is sufficient to alleviate cognition deficits and depressive behavior in 6-OHDA lesioned rats and long-term treatment reduces the progression of motor symptoms and elevates tyrosine hydroxylase (TH, Brain-derived neurotrophic factor (BDNF, bone marrow tyrosine kinase in chromosome X (BMX protein expression level without affecting dopaminergic (DA neuron loss in this PD rat model.

Milk fat globule membrane supplementation with voluntary running exercise attenuates age-related motor dysfunction by suppressing neuromuscular junction abnormalities in mice.

Science.gov (United States)

Yano, Michiko; Minegishi, Yoshihiko; Sugita, Satoshi; Ota, Noriyasu

2017-10-15

Age-related loss of skeletal muscle mass and function attenuates physical performance, and maintaining fine muscle innervation is known to play an important role in its prevention. We had previously shown that consumption of milk fat globule membrane (MFGM) with habitual exercise improves the muscle mass and motor function in humans and mice. Improvement of neuromuscular junction (NMJ) was suggested as one of the mechanisms underlying these effects. In this study, we evaluated the effect of MFGM intake combined with voluntary running (MFGM-VR) on morphological changes of NMJ and motor function in aging mice. Seven months following the intervention, the MFGM-VR group showed a significantly improved motor coordination in the rotarod test and muscle force in the grip strength test compared with the control group at 13 and 14months of age, respectively. In 14-month old control mice, the extensor digitorum longus muscle showed increased abnormal NMJs, such as fragmentation and denervation, compared with 6-month old young mice. However, such age-related deteriorations of NMJs were significantly suppressed in the MFGM-VR group. Increase in the expression of NMJ formation-related genes, such as agrin and LDL Receptor Related Protein 4 (LRP4), might contribute to this beneficial effect. Rotarod performance and grip strength showed significant negative correlation with the status of denervation and fragmentation of NMJs. These results suggest that MFGM intake with voluntary running exercise effectively suppresses age-related morphological deterioration of NMJ, thus contributing to improvement of motor function. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

TECHNO-ECONOMIC ASSESSMENT OF THE USE OF WHEELS OF PERSPECTIVE STRUCTURAL SCHEME FOR RAILWAY VEHICLES

Directory of Open Access Journals (Sweden)

S. A. Semenov

2016-12-01

, used in running gear of railway vehicles were substantiated. Practical value. The calculation method proposed in this publication allows evaluating the technical and economic feasibility of using the wheels of promising design scheme in the running gears of railway vehicles.

Prediction of the comparative reinforcement values of running and drinking.

Science.gov (United States)

PREMACK, D

1963-03-15

The probability of free drinking and running in rats was controlled by sucrose concentration and force requirements on an activity wheel. Drinking and running were then made contingent on pressing a bar. Barpressing increased monotonically with the associated response probability, and equally for drinking and running. The results support the assumption that different responses of equal probability have equal reinforcement value.

Depletion of Pax7+ satellite cells does not affect diaphragm adaptations to running in young or aged mice.

Science.gov (United States)

Murach, Kevin A; Confides, Amy L; Ho, Angel; Jackson, Janna R; Ghazala, Lina S; Peterson, Charlotte A; Dupont-Versteegden, Esther E

2017-10-01

Satellite cell depletion does not affect diaphragm adaptations to voluntary wheel running in young or aged mice. Satellite cell depletion early in life (4 months of age) has minimal effect on diaphragm phenotype by old age (24 months). Prolonged satellite cell depletion in the diaphragm does not result in excessive extracellular matrix accumulation, in contrast to what has been reported in hind limb muscles. Up-regulation of Pax3 mRNA+ cells after satellite cell depletion in young and aged mice suggests that Pax3+ cells may compensate for a loss of Pax7+ satellite cells in the diaphragm. Future investigations should focus on the role of Pax3+ cells in the diaphragm during adaptation to exercise and ageing. Satellite cell contribution to unstressed diaphragm is higher compared to hind limb muscles, which is probably attributable to constant activation of this muscle to drive ventilation. Whether satellite cell depletion negatively impacts diaphragm quantitative and qualitative characteristics under stressed conditions in young and aged mice is unknown. We therefore challenged the diaphragm with prolonged running activity in the presence and absence of Pax7+ satellite cells in young and aged mice using an inducible Pax7 CreER -R26R DTA model. Mice were vehicle (Veh, satellite cell-replete) or tamoxifen (Tam, satellite cell-depleted) treated at 4 months of age and were then allowed to run voluntarily at 6 months (young) and 22 months (aged). Age-matched, cage-dwelling, Veh- and Tam-treated mice without wheel access served as activity controls. Diaphragm muscles were analysed from young (8 months) and aged (24 months) mice. Satellite cell depletion did not alter diaphragm mean fibre cross-sectional area, fibre type distribution or extracellular matrix content in young or aged mice, regardless of running activity. Resting in vivo diaphragm function was also unaffected by satellite cell depletion. Myonuclear density was maintained in young satellite cell

Skin blister formation together with patterned intradermal hematoma: a special type of tire mark injury in victims run over by a wheel.

Science.gov (United States)

Pircher, R; Epting, T; Schmidt, U; Geisenberger, D; Pollak, S; Kramer, L

2015-04-01

A traffic accident victim run over by a vehicle may show a patterned skin hematoma reflecting the grooves of the tire's profile. Apart from this well-known type of imprint mark, the affected skin can also be blistered provided that the wheel exerts high pressure on the body for a prolonged period of time. The macro- and micromorphological findings as well as the protein composition of the blister fluid were investigated on the basis of a relevant autopsy case. Analogous to blisters associated with hanging marks, the transudation of serous fluid with consecutive detachment of the epidermis is interpreted as a pressure-related effect which cannot be regarded as a sign of vitality. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and Methylone

Science.gov (United States)

Aarde, Shawn M.; Miller, Michelle L.; Creehan, Kevin M.; Vandewater, Sophia A.; Taffe, Michael A.

2015-01-01

Background Exercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation. Methods Rats were trained in the intravenous self-administration (IVSA) of d-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ~22 hrs of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design. Results Provision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual’s decrease in drug intake. Conclusions Wheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern. PMID:25863714

Development of free running differential. Development of differential with an actuator and a clutch which disconnects the traction; Free running defu no kaihatsu. Kirippanashi kiko oyobi actuator wo naizoshita differential sochi no kaihatsu

Energy Technology Data Exchange (ETDEWEB)

Yamazaki, N; Teraoka, M; Ishikawa, O; Nagaoka, T; Ugajin, K [Tochigi Fuji Sangyo Co. Ltd., Tochigi (Japan)

1997-10-01

Free Running Differential has an effect on fuel economy and noise reduction from drive line for four wheel drive vehicle. It has an actuator and a clutch which disconnects the traction from no driving side tire when two wheel drive is selected. this unit can be installed in conventional differential carrier with no design change. It is compact in design and low in cost. We evaluate it as having a dominant position among any other Free running system. 7 figs.

Mechanical Design Engineering Enabler Project wheel and wheel drives

Science.gov (United States)

Nutt, Richard E.; Couch, Britt K.; Holley, John L., Jr.; Garris, Eric S.; Staut, Paul V.

1992-01-01

Our group was assigned the responsibility of designing the wheel and wheel drive system for a proof-of-concept model of the lunar-based ENABLER. ENABLER is a multi-purpose, six wheeled vehicle designed to lift and transport heavy objects associated with the construction of a lunar base. The resulting design was based on the performance criteria of the ENABLER. The drive system was designed to enable the vehicle to achieve a speed of 7 mph on a level surface, climb a 30 percent grade, and surpass a one meter high object and one meter wide crevice. The wheel assemblies were designed to support the entire weight of the vehicle on two wheels. The wheels were designed to serve as the main component of the vehicle's suspension and will provide suitable traction for lunar-type surfaces. The expected performance of the drive system for the ENABLER was influenced by many mechanical factors. The expected top speed on a level sandy surface is 4 mph instead of the desired 7 mph. This is due to a lack of necessary power at the wheels. The lack of power resulted from dimension considerations that allowed only an eight horsepower engine and also from mechanical inefficiencies of the hydraulic system. However, the vehicle will be able to climb a 30 percent grade, surpass a one meter high object and one meter wide crevice. The wheel assemblies will be able to support the entire weight of the vehicle on two wheels. The wheels will also provide adequate suspension for the vehicle and sufficient traction for lunar-type surfaces.

RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus.

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Grégoire, Catherine-Alexandra; Tobin, Stephanie; Goldenstein, Brianna L; Samarut, Éric; Leclerc, Andréanne; Aumont, Anne; Drapeau, Pierre; Fulton, Stephanie; Fernandes, Karl J L

2018-01-01

Environmental enrichment (EE) is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG), a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN), a locked disk (LD), or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE)]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running's genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

Integration of uniform design and quantum-behaved particle swarm optimization to the robust design for a railway vehicle suspension system under different wheel conicities and wheel rolling radii

Science.gov (United States)

Cheng, Yung-Chang; Lee, Cheng-Kang

2017-10-01

This paper proposes a systematic method, integrating the uniform design (UD) of experiments and quantum-behaved particle swarm optimization (QPSO), to solve the problem of a robust design for a railway vehicle suspension system. Based on the new nonlinear creep model derived from combining Hertz contact theory, Kalker's linear theory and a heuristic nonlinear creep model, the modeling and dynamic analysis of a 24 degree-of-freedom railway vehicle system were investigated. The Lyapunov indirect method was used to examine the effects of suspension parameters, wheel conicities and wheel rolling radii on critical hunting speeds. Generally, the critical hunting speeds of a vehicle system resulting from worn wheels with different wheel rolling radii are lower than those of a vehicle system having original wheels without different wheel rolling radii. Because of worn wheels, the critical hunting speed of a running railway vehicle substantially declines over the long term. For safety reasons, it is necessary to design the suspension system parameters to increase the robustness of the system and decrease the sensitive of wheel noises. By applying UD and QPSO, the nominal-the-best signal-to-noise ratio of the system was increased from -48.17 to -34.05 dB. The rate of improvement was 29.31%. This study has demonstrated that the integration of UD and QPSO can successfully reveal the optimal solution of suspension parameters for solving the robust design problem of a railway vehicle suspension system.

Inhibition of progression of androgen-dependent prostate LNCaP tumors to androgen independence in SCID mice by oral caffeine and voluntary exercise.

Science.gov (United States)

Zheng, Xi; Cui, Xiao-Xing; Huang, Mou-Tuan; Liu, Yue; Wagner, George C; Lin, Yong; Shih, Weichung Joe; Lee, Mao-Jung; Yang, Chung S; Conney, Allan H

2012-01-01

The effect of oral caffeine or voluntary running wheel exercise (RW) alone or in combination on the progression of human androgen-dependent LNCaP prostate tumors to androgen independence in male severe combined immunodeficiency mice was determined. The mice were injected subcutaneously with LNCaP cells, and when the tumors reached a moderate size, the mice were surgically castrated and treated with caffeine (0.40 mg/ml drinking water) or RW alone or in combination for 42 days. We found that caffeine administration or RW inhibited the progression and growth of androgen-dependent LNCaP tumors to androgen independence, and a combination of the 2 regimens was more effective than the individual regimens alone. The ratios of the percent mitotic cells/caspase-3 positive cells in tumors from the caffeine-treated, RW-treated, or combination-treated mice were decreased by 34%, 38%, and 52%, respectively. Caffeine treatment increased the percentage of mitotic tumor cells undergoing apoptosis (lethal mitosis) whereas RW inhibited the increase in interleukin-6 that occurred during the progression of LNCaP tumors from androgen dependence to androgen independence. Our results indicate that oral administration of caffeine in combination with voluntary exercise may be an effective strategy for the prevention of prostate cancer progression from androgen dependence to androgen independence.

Concurrent schedules of wheel-running reinforcement: choice between different durations of opportunity to run in rats.

Science.gov (United States)

Belke, Terry W

2006-02-01

How do animals choose between opportunities to run of different durations? Are longer durations preferred over shorter durations because they permit a greater number of revolutions? Are shorter durations preferred because they engender higher rates of running? Will longer durations be chosen because running is less constrained? The present study reports on three experiments that attempted to address these questions. In the first experiment, five male Wistar rats chose between 10-sec and 50-sec opportunities to run on modified concurrent variable-interval (VI) schedules. Across conditions, the durations associated with the alternatives were reversed. Response, time, and reinforcer proportions did not vary from indifference. In a second experiment, eight female Long-Evans rats chose between opportunities to run of equal (30 sec) and unequal durations (10 sec and 50 sec) on concurrent variable-ratio (VR) schedules. As in Experiment 1, between presentations of equal duration conditions, 10-sec and 50-sec durations were reversed. Results showed that response, time, and reinforcer proportions on an alternative did not vary with reinforcer duration. In a third experiment, using concurrent VR schedules, durations were systematically varied to decrease the shorter duration toward 0 sec. As the shorter duration decreased, response, time, and reinforcer proportions shifted toward the longer duration. In summary, differences in durations of opportunities to run did not affect choice behavior in a manner consistent with the assumption that a longer reinforcer is a larger reinforcer.

Untangling the influences of voluntary running, environmental complexity, social housing and stress on adult hippocampal neurogenesis.

Directory of Open Access Journals (Sweden)

Catherine-Alexandra Grégoire

Full Text Available Environmental enrichment (EE exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel "Alternating EE" paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1 voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2 a complex environment (comprised of both social interactions and rotated inanimate objects had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects; and (3 neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this "Alternating EE" paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity.

Untangling the Influences of Voluntary Running, Environmental Complexity, Social Housing and Stress on Adult Hippocampal Neurogenesis

Science.gov (United States)

Grégoire, Catherine-Alexandra; Bonenfant, David; Le Nguyen, Adalie; Aumont, Anne; Fernandes, Karl J. L.

2014-01-01

Environmental enrichment (EE) exerts powerful effects on brain physiology, and is widely used as an experimental and therapeutic tool. Typical EE paradigms are multifactorial, incorporating elements of physical exercise, environmental complexity, social interactions and stress, however the specific contributions of these variables have not been separable using conventional housing paradigms. Here, we evaluated the impacts of these individual variables on adult hippocampal neurogenesis by using a novel “Alternating EE” paradigm. For 4 weeks, adult male CD1 mice were alternated daily between two enriched environments; by comparing groups that differed in one of their two environments, the individual and combinatorial effects of EE variables could be resolved. The Alternating EE paradigm revealed that (1) voluntary running for 3 days/week was sufficient to increase both mitotic and post-mitotic stages of hippocampal neurogenesis, confirming the central importance of exercise; (2) a complex environment (comprised of both social interactions and rotated inanimate objects) had no effect on neurogenesis itself, but enhanced depolarization-induced c-Fos expression (attributable to social interactions) and buffered stress-induced plasma corticosterone levels (attributable to inanimate objects); and (3) neither social isolation, group housing, nor chronically increased levels of plasma corticosterone had a prolonged impact on neurogenesis. Mouse strain, handling and type of running apparatus were tested and excluded as potential confounding factors. These findings provide valuable insights into the relative effects of key EE variables on adult neurogenesis, and this “Alternating EE” paradigm represents a useful tool for exploring the contributions of individual EE variables to mechanisms of neural plasticity. PMID:24465980

Maternal Voluntary Exercise during Pregnancy Enhances the Spatial Learning Acquisition but not the Retention of Memory in Rat Pups via a TrkB-mediated Mechanism: The Role of Hippocampal BDNF Expression

Directory of Open Access Journals (Sweden)

Maziar M Akhavan

2013-09-01

Full Text Available   Objective(s: The effect of maternal voluntary exercise on hippocampal BDNF level in rat offspring was studied. In addition, the possible role of hippocampal BDNF receptors in maternal exercise induced enhancement of learning in the rat pups was investigated.   Materials and Methods: Pregnant rats have been randomly assigned to sedentary control or voluntary exercise groups. Each of the exercising pregnant rats was given access to a cage that was equipped with a running wheel until the end of their pregnancy. On post natal day (PND 36, two groups consisted of 7 male rat pups in each group from sedentary or exercised mothers were sacrificed and the hippocampus was dissected for BDNF proteins level determination. Also, bilateral injection of K252a to the hippocampus was used to block the hippocampal BDNF action on PND59 in the rat pups. Results: Voluntary exercise during pregnancy significantly increased the level of BDNF protein in the hippocampus of the rat pups on PND36 compared to the control group (P=0.048. Inhibiting BDNF action abolished the exercise-induced improvement of learning acquisition in offspring in training trials (P=0.0001. No difference was observed in the platform location latency and the time spent in the target in the probe test between two groups. Conclusion : This study demonstrates that voluntary exercise during pregnancy via a TrkB-mediated mechanism enhances the spatial learning acquisition, however, not the retention of memory in the rat pups.

RNA-Sequencing Reveals Unique Transcriptional Signatures of Running and Running-Independent Environmental Enrichment in the Adult Mouse Dentate Gyrus

Directory of Open Access Journals (Sweden)

Catherine-Alexandra Grégoire

2018-04-01

Full Text Available Environmental enrichment (EE is a powerful stimulus of brain plasticity and is among the most accessible treatment options for brain disease. In rodents, EE is modeled using multi-factorial environments that include running, social interactions, and/or complex surroundings. Here, we show that running and running-independent EE differentially affect the hippocampal dentate gyrus (DG, a brain region critical for learning and memory. Outbred male CD1 mice housed individually with a voluntary running disk showed improved spatial memory in the radial arm maze compared to individually- or socially-housed mice with a locked disk. We therefore used RNA sequencing to perform an unbiased interrogation of DG gene expression in mice exposed to either a voluntary running disk (RUN, a locked disk (LD, or a locked disk plus social enrichment and tunnels [i.e., a running-independent complex environment (CE]. RNA sequencing revealed that RUN and CE mice showed distinct, non-overlapping patterns of transcriptomic changes versus the LD control. Bio-informatics uncovered that the RUN and CE environments modulate separate transcriptional networks, biological processes, cellular compartments and molecular pathways, with RUN preferentially regulating synaptic and growth-related pathways and CE altering extracellular matrix-related functions. Within the RUN group, high-distance runners also showed selective stress pathway alterations that correlated with a drastic decline in overall transcriptional changes, suggesting that excess running causes a stress-induced suppression of running’s genetic effects. Our findings reveal stimulus-dependent transcriptional signatures of EE on the DG, and provide a resource for generating unbiased, data-driven hypotheses for novel mediators of EE-induced cognitive changes.

RUN COORDINATION

CERN Multimedia

M. Chamizo

2012-01-01

  On 17th January, as soon as the services were restored after the technical stop, sub-systems started powering on. Since then, we have been running 24/7 with reduced shift crew — Shift Leader and DCS shifter — to allow sub-detectors to perform calibration, noise studies, test software upgrades, etc. On 15th and 16th February, we had the first Mid-Week Global Run (MWGR) with the participation of most sub-systems. The aim was to bring CMS back to operation and to ensure that we could run after the winter shutdown. All sub-systems participated in the readout and the trigger was provided by a fraction of the muon systems (CSC and the central RPC wheel). The calorimeter triggers were not available due to work on the optical link system. Initial checks of different distributions from Pixels, Strips, and CSC confirmed things look all right (signal/noise, number of tracks, phi distribution…). High-rate tests were done to test the new CSC firmware to cure the low efficiency ...

High and low nightly running behavior associates with nucleus accumbens N-Methyl-d-aspartate receptor (NMDAR) NR1 subunit expression and NMDAR functional differences.

Science.gov (United States)

Grigsby, Kolter B; Kovarik, Cathleen M; Rottinghaus, George E; Booth, Frank W

2018-04-03

The extent to which N-Methyl-d-aspartate (NMDA) receptors facilitate the motivation to voluntarily wheel-run in rodents has yet to be determined. In so, we utilized female Wistar rats selectively bred to voluntarily run high (HVR) and low (LVR) nightly distances in order to examine if endogenous differences in nucleus accumbens (NAc) NMDA receptor expression and function underlies the propensity for high or low motivation to voluntarily wheel-run. 12-14 week old HVR and LVR females were used to examine: 1.) NAc mRNA and protein expression of NMDA subunits NR1, NR2A and NR2B; 2.) NMDA current responses in isolated medium spiny neurons (MSNs) and 3.) NMDA-evoked dopamine release in an ex vivo preparation of NAc punches. Expectedly, there was a large divergence in nightly running distance and time between HVR and LVR rats. We saw a significantly higher mRNA and protein expression of NR1 in HVR compared to LVR rats, while seeing no difference in the expression of NR2A or NR2B. There was a greater current response to a 500 ms application of 300 μM of NMDA in medium-spiny neurons isolated from the NAc HVR compared to LVR animals. On average, NMDA-evoked punches (50 μM of NMDA for 10 min) taken from HVR rats retained ∼54% of the dopamine content compared to their bilateral non-evoked sides, while evoked punches from LVR animals showed no statistical decrease in dopamine content compared to their non-evoked sides. Collectively, these data suggest a potential link between NAc NR1 subunit expression as well as NMDA function and the predisposition for nightly voluntary running behavior in rats. In light of the epidemic rise in physical inactivity, these findings have the potential to explain a neuro-molecular mechanism that regulates the motivation to be physically active. Copyright © 2018 Elsevier B.V. All rights reserved.

Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages.

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Kizaki, Takako; Maegawa, Taketeru; Sakurai, Takuya; Ogasawara, Jun-etsu; Ookawara, Tomomi; Oh-ishi, Shuji; Izawa, Tetsuya; Haga, Shukoh; Ohno, Hideki

2011-09-30

Chronic low-level inflammation is associated with obesity and a sedentary lifestyle, causing metabolic disturbances such as insulin resistance. Exercise training has been shown to decrease chronic low-level systemic inflammation in high-fat diet (HFD)-induced obesity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Ghrelin is a peptide hormone predominantly produced in the stomach that stimulates appetite and induces growth hormone release. In addition to these well-known functions, recent studies suggest that ghrelin localizes to immune cells and exerts an anti-inflammatory effect. The purpose of the current study was to investigate the role of ghrelin expressed in macrophages in the anti-inflammatory effects of voluntary exercise training. Expression of tumor necrosis factor-α (TNF-α), monocyte chemotactic protein (MCP)-1 and F4/80 was increased in adipose tissue from mice fed a HFD (HFD mice) compared with mice fed a standard diet (SD mice), whereas the expression of these inflammatory cytokines was markedly decreased in mice performing voluntary wheel running during the feeding of a HFD (HFEx mice). The expression of TNF-α was also increased in peritoneal macrophages by a HFD and exercise training inhibited the increase of TNF-α expression. Interestingly, expression of ghrelin in peritoneal macrophages was decreased by a HFD and recovered by exercise training. Suppression of ghrelin expression by siRNA increased TNF-α expression and LPS-stimulated NF-κB activation in RAW264 cells, which is a macrophage cell line. TNF-α expression by stimulation with LPS was significantly suppressed in RAW264 cells cultured in the presence of ghrelin. These results suggest that ghrelin exerts potent anti-inflammatory effects in macrophages and functions as a mediator of the beneficial effects of exercise training. Copyright © 2011 Elsevier Inc. All rights reserved.

Origami Wheel Transformer: A Variable-Diameter Wheel Drive Robot Using an Origami Structure.

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Lee, Dae-Young; Kim, Sa-Reum; Kim, Ji-Suk; Park, Jae-Jun; Cho, Kyu-Jin

2017-06-01

A wheel drive mechanism is simple, stable, and efficient, but its mobility in unstructured terrain is seriously limited. Using a deformable wheel is one of the ways to increase the mobility of a wheel drive robot. By changing the radius of its wheels, the robot becomes able to pass over not only high steps but also narrow gaps. In this article, we propose a novel design for a variable-diameter wheel using an origami-based soft robotics design approach. By simply folding a patterned sheet into a wheel shape, a variable-diameter wheel was built without requiring lots of mechanical parts and a complex assembly process. The wheel's diameter can change from 30 to 68 mm, and it is light in weight at about 9.7 g. Although composed of soft materials (fabrics and films), the wheel can bear more than 400 times its weight. The robot was able to change the wheel's radius in response to terrain conditions, allowing it to pass over a 50-mm gap when the wheel is shrunk and a 50-mm step when the wheel is enlarged.

The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model.

Directory of Open Access Journals (Sweden)

Zheng Ke

Full Text Available BACKGROUND: Stroke rehabilitation with different exercise paradigms has been investigated, but which one is more effective in facilitating motor recovery and up-regulating brain neurotrophic factor (BDNF after brain ischemia would be interesting to clinicians and patients. Voluntary exercise, forced exercise, and involuntary muscle movement caused by functional electrical stimulation (FES have been individually demonstrated effective as stroke rehabilitation intervention. The aim of this study was to investigate the effects of these three common interventions on brain BDNF changes and motor recovery levels using a rat ischemic stroke model. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and seventeen Sprague-Dawley rats were randomly distributed into four groups: Control (Con, Voluntary exercise of wheel running (V-Ex, Forced exercise of treadmill running (F-Ex, and Involuntary exercise of FES (I-Ex with implanted electrodes placed in two hind limb muscles on the affected side to mimic gait-like walking pattern during stimulation. Ischemic stroke was induced in all rats with the middle cerebral artery occlusion/reperfusion model and fifty-seven rats had motor deficits after stroke. Twenty-four hours after reperfusion, rats were arranged to their intervention programs. De Ryck's behavioral test was conducted daily during the 7-day intervention as an evaluation tool of motor recovery. Serum corticosterone concentration and BDNF levels in the hippocampus, striatum, and cortex were measured after the rats were sacrificed. V-Ex had significantly better motor recovery in the behavioral test. V-Ex also had significantly higher hippocampal BDNF concentration than F-Ex and Con. F-Ex had significantly higher serum corticosterone level than other groups. CONCLUSION/SIGNIFICANCE: Voluntary exercise is the most effective intervention in upregulating the hippocampal BDNF level, and facilitating motor recovery. Rats that exercised voluntarily also showed less

Vehicle Dynamics Control of In-wheel Electric Motor Drive Vehicles Based on Averaging of Tire Force Usage

Science.gov (United States)

Masaki, Nobuo; Iwano, Haruo; Kamada, Takayoshi; Nagai, Masao

For in-wheel electric motor drive vehicles, a new vehicle dynamics control which is based on the tire force usage rate is proposed. The new controller adopts non-linear optimal control could manage the interference between direct yaw-moment control and the tire force usage rate. The new control is considered total longitudinal and transverse tire force. Therefore the controller can prevent tire force saturation near tire force limit during cornering. Simulations and test runs by the custom made four wheel drive in-wheel motor electric vehicle show that higher driving stability performance compared to the performance of the same vehicle without control.

Differential effects of voluntary wheel running and toy rotation on the mRNA expression of neurotrophic factors and FKBP5 in a post-traumatic stress disorder rat model with the shuttle-box task.

Science.gov (United States)

Tanichi, Masaaki; Toda, Hiroyuki; Shimizu, Kunio; Koga, Minori; Saito, Taku; Enomoto, Shingo; Boku, Shuken; Asai, Fumiho; Mitsui, Yumi; Nagamine, Masanori; Fujita, Masanori; Yoshino, Aihide

2018-06-18

Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the differential effects of EE components, i.e., running wheel (RW) or toy rotation, on PTSD-like behaviors has remained unclear. In this experiment, we demonstrated that RW, toy rotation, and EE (containing RW and toy rotation) ameliorated avoidance/numbing-like behaviors, induced learning of avoidance responses, and improved depressive-like behaviors in traumatized rats. The RW increased the hippocampal mRNA expression of neurotrophic factors, especially BDNF and glial-cell derived neurotrophic factor. Toy rotation influenced FK506 binding protein 5 mRNA expression, which is believed to be a regulator of the hypothalamic-pituitary-adrenal (HPA)-axis system, in the hippocampus and amygdala. This is the first report to elucidate the differential mechanistic effects of RW and toy rotation. The former appears to exert its effects via neurotrophic factors, while the latter exerts its effects via the HPA axis. Further studies will lead to a better understanding of the influence of environmental factors on PTSD. Copyright © 2018 Elsevier Inc. All rights reserved.

Online measurement for geometrical parameters of wheel set based on structure light and CUDA parallel processing

Science.gov (United States)

Wu, Kaihua; Shao, Zhencheng; Chen, Nian; Wang, Wenjie

2018-01-01

The wearing degree of the wheel set tread is one of the main factors that influence the safety and stability of running train. Geometrical parameters mainly include flange thickness and flange height. Line structure laser light was projected on the wheel tread surface. The geometrical parameters can be deduced from the profile image. An online image acquisition system was designed based on asynchronous reset of CCD and CUDA parallel processing unit. The image acquisition was fulfilled by hardware interrupt mode. A high efficiency parallel segmentation algorithm based on CUDA was proposed. The algorithm firstly divides the image into smaller squares, and extracts the squares of the target by fusion of k_means and STING clustering image segmentation algorithm. Segmentation time is less than 0.97ms. A considerable acceleration ratio compared with the CPU serial calculation was obtained, which greatly improved the real-time image processing capacity. When wheel set was running in a limited speed, the system placed alone railway line can measure the geometrical parameters automatically. The maximum measuring speed is 120km/h.

On the non-proportionality between wheel/rail contact forces and speed during wheelset passage over specific welds

Science.gov (United States)

Correa, Nekane; Vadillo, Ernesto G.; Santamaria, Javier; Blanco-Lorenzo, Julio

2018-01-01

This study investigates the influence on the wheel-rail contact forces of the running speed and the shape and position of weld defects along the track. For this purpose, a vertical dynamic model in the space domain is used. The model is obtained from the transformation between the domains of frequency and space using a Rational Fraction Polynomials (RFP) method, which is modified with multiobjective genetic algorithms in order to improve the fitting of track receptance and to assist integration during simulations. This produces a precise model with short calculation times, which is essential to this study. The wheel-rail contact is modelled using a non-linear Hertz spring. The contact forces are studied for several types of characteristic welds. The way in which forces vary as a function of weld position and running speed is studied for each type of weld. This paper studies some of the factors that affect the maximum forces when the vehicle moves over a rail weld, such as weld geometry, parametric excitation and contact stiffness. It is found that the maximum force in the wheel-rail contact when the vehicle moves over a weld is not always proportional to the running speed. The paper explains why it is not proportional in specific welds.

Role of the dorsal medial habenula in the regulation of voluntary activity, motor function, hedonic state, and primary reinforcement.

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Hsu, Yun-Wei A; Wang, Si D; Wang, Shirong; Morton, Glenn; Zariwala, Hatim A; de la Iglesia, Horacio O; Turner, Eric E

2014-08-20

The habenular complex in the epithalamus consists of distinct regions with diverse neuronal populations. Past studies have suggested a role for the habenula in voluntary exercise motivation and reinforcement of intracranial self-stimulation but have not assigned these effects to specific habenula subnuclei. Here, we have developed a genetic model in which neurons of the dorsal medial habenula (dMHb) are developmentally eliminated, via tissue-specific deletion of the transcription factor Pou4f1 (Brn3a). Mice with dMHb lesions perform poorly in motivation-based locomotor behaviors, such as voluntary wheel running and the accelerating rotarod, but show only minor abnormalities in gait and balance and exhibit normal levels of basal locomotion. These mice also show deficits in sucrose preference, but not in the forced swim test, two measures of depression-related phenotypes in rodents. We have also used Cre recombinase-mediated expression of channelrhodopsin-2 and halorhodopsin to activate dMHb neurons or silence their output in freely moving mice, respectively. Optical activation of the dMHb in vivo supports intracranial self-stimulation, showing that dMHb activity is intrinsically reinforcing, whereas optical silencing of dMHb outputs is aversive. Together, our findings demonstrate that the dMHb is involved in exercise motivation and the regulation of hedonic state, and is part of an intrinsic reinforcement circuit. Copyright © 2014 the authors 0270-6474/14/3411366-19$15.00/0.

Adolescent voluntary exercise attenuated hippocampal innate immunity responses and depressive-like behaviors following maternal separation stress in male rats.

Science.gov (United States)

Sadeghi, Mahsa; Peeri, Maghsoud; Hosseini, Mir-Jamal

2016-09-01

Early life stressful events have detrimental effects on the brain and behavior, which are associated with the development of depression. Immune-inflammatory responses have been reported to contribute in the pathophysiology of depression. Many studies have reported on the beneficial effects of exercise against stress. However, underlying mechanisms through which exercise exerts its effects were poorly studied. Therefore, it applied maternal separation (MS), as a valid animal model of early-life adversity, in rats from postnatal day (PND) 2 to 14 for 180min per day. At PND 28, male Wistar albino rats were subjected to 5 experimental groups; 1) controls 2) MS rats 3) MS rats treated with fluoxetine 5mg/kg to PND 60, 4) MS rats that were subjected to voluntary running wheel (RW) exercise and 5) MS rats that were subjected to mandatory treadmill (TM) exercise until adulthood. At PND 60, depressive-like behaviors were assessed by using forced swimming test (FST), splash test, and sucrose preference test (SPT). Our results revealed that depressive-like behaviors following MS stress were associated with an increase in expression of toll-like receptor 4 (Tlr-4) and its main signaling protein, Myd88, in the hippocampal formation. Also, we found that voluntary (and not mandatory) physical exercise during adolescence is protected against depressant effects of early-life stress at least partly through mitigating the innate immune responses in the hippocampus. Copyright © 2016. Published by Elsevier Inc.

Delivery mechanisms: voluntary vs command and control

International Nuclear Information System (INIS)

Kierans, T.

1997-01-01

The success of Canada's Voluntary Challenge and Registry (VCR) program was debated. The generally accepted view is that the voluntary program to stabilize greenhouse gas emissions at 1990 levels by year 2000 has failed. However, the author suggested that the issues and processes are complicated and that we should not give up too soon. Time is needed to refine the market instruments that we are dealing with. Also, there are substantial economic barriers to fully meet target figures, among them the fact that municipalities, universities, social services and health care industries are chronically capital rationed and don't have the money to respond to the VCR program. Other sectors of the economy capitalized and regulated by government, have not seen much success in the VCR program either. The central argument is that while voluntary programs are probably not the answer, binding agreements or government-run schemes are even less likely to succeed

Cerebral vascular structure in the motor cortex of adult mice is stable and is not altered by voluntary exercise.

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Cudmore, Robert H; Dougherty, Sarah E; Linden, David J

2017-12-01

The cerebral vasculature provides blood flow throughout the brain, and local changes in blood flow are regulated to match the metabolic demands of the active brain regions. This neurovascular coupling is mediated by real-time changes in vessel diameter and depends on the underlying vascular network structure. Neurovascular structure is configured during development by genetic and activity-dependent factors. In adulthood, it can be altered by experiences such as prolonged hypoxia, sensory deprivation and seizure. Here, we have sought to determine whether exercise could alter cerebral vascular structure in the adult mouse. We performed repeated in vivo two-photon imaging in the motor cortex of adult transgenic mice expressing membrane-anchored green fluorescent protein in endothelial cells (tyrosine endothelial kinase 2 receptor (Tie2)-Cre:mTmG). This strategy allows for high-resolution imaging of the vessel walls throughout the lifespan. Vascular structure, as measured by capillary branch point number and position, segment diameter and length remained stable over a time scale of months as did pericyte number and position. Furthermore, we compared the vascular structure before, during, and after periods of voluntary wheel running and found no alterations in these same parameters. In both running and control mice, we observed a low rate of capillary segment subtraction. Interestingly, these rare subtraction events preferentially remove short vascular loops.

Estimating the Backup Reaction Wheel Orientation Using Reaction Wheel Spin Rates Flight Telemetry from a Spacecraft

Science.gov (United States)

Rizvi, Farheen

2013-01-01

A report describes a model that estimates the orientation of the backup reaction wheel using the reaction wheel spin rates telemetry from a spacecraft. Attitude control via the reaction wheel assembly (RWA) onboard a spacecraft uses three reaction wheels (one wheel per axis) and a backup to accommodate any wheel degradation throughout the course of the mission. The spacecraft dynamics prediction depends upon the correct knowledge of the reaction wheel orientations. Thus, it is vital to determine the actual orientation of the reaction wheels such that the correct spacecraft dynamics can be predicted. The conservation of angular momentum is used to estimate the orientation of the backup reaction wheel from the prime and backup reaction wheel spin rates data. The method is applied in estimating the orientation of the backup wheel onboard the Cassini spacecraft. The flight telemetry from the March 2011 prime and backup RWA swap activity on Cassini is used to obtain the best estimate for the backup reaction wheel orientation.

Synaptic Remodeling in the Dentate Gyrus, CA3, CA1, Subiculum, and Entorhinal Cortex of Mice: Effects of Deprived Rearing and Voluntary Running

Directory of Open Access Journals (Sweden)

Andrea T. U. Schaefers

2010-01-01

Full Text Available Hippocampal cell proliferation is strongly increased and synaptic turnover decreased after rearing under social and physical deprivation in gerbils (Meriones unguiculatus. We examined if a similar epigenetic effect of rearing environment on adult neuroplastic responses can be found in mice (Mus musculus. We examined synaptic turnover rates in the dentate gyrus, CA3, CA1, subiculum, and entorhinal cortex. No direct effects of deprived rearing on rates of synaptic turnover were found in any of the studied regions. However, adult wheel running had the effect of leveling layer-specific differences in synaptic remodeling in the dentate gyrus, CA3, and CA1, but not in the entorhinal cortex and subiculum of animals of both rearing treatments. Epigenetic effects during juvenile development affected adult neural plasticity in mice, but seemed to be less pronounced than in gerbils.

The response of a high-speed train wheel to a harmonic wheel-rail force

International Nuclear Information System (INIS)

Sheng, Xiaozhen; Liu, Yuxia; Zhou, Xin

2016-01-01

The maximum speed of China's high-speed trains currently is 300km/h and expected to increase to 350-400km/h. As a wheel travels along the rail at such a high speed, it is subject to a force rotating at the same speed along its periphery. This fast moving force contains not only the axle load component, but also many components of high frequencies generated from wheel-rail interactions. Rotation of the wheel also introduces centrifugal and gyroscopic effects. How the wheel responds is fundamental to many issues, including wheel-rail contact, traction, wear and noise. In this paper, by making use of its axial symmetry, a special finite element scheme is developed for responses of a train wheel subject to a vertical and harmonic wheel-rail force. This FE scheme only requires a 2D mesh over a cross-section containing the wheel axis but includes all the effects induced by wheel rotation. Nodal displacements, as a periodic function of the cross-section angle 6, can be decomposed, using Fourier series, into a number of components at different circumferential orders. The derived FE equation is solved for each circumferential order. The sum of responses at all circumferential orders gives the actual response of the wheel. (paper)

AMPKα in Exercise-Induced Substrate Metabolism and Exercise Training-Induced Metabolic and Mitochondrial Adaptations

DEFF Research Database (Denmark)

Fentz, Joachim

in response to 4 weeks of voluntary running wheel exercise training. However, the acute exercise-induced increase in mRNA expression of several metabolic and mitochondrial marker genes is impaired in the mice lacking AMPKα1 and α2. In addition to the two studies and some currently unpublished data this thesis...

Decreased spontaneous activity in AMPK alpha 2 muscle specific kinase dead mice is not caused by changes in brain dopamine metabolism

DEFF Research Database (Denmark)

Møller, Lisbeth Liliendal Valbjørn; Sylow, Lykke; Gøtzsche, Casper René

2016-01-01

was tested in an open field test. Furthermore, we investigated maximal running capacity and voluntary running over a period of 19 days. AMPK α2 KD mice ran 30% less in daily distance compared to WT. Furthermore, AMPK α2 KD mice showed significantly decreased locomotor activity in the open field test compared...... through alterations of the brain dopamine levels specifically in the striatal region. To test this hypothesis, transgenic mice overexpressing an inactivatable dominant negative α2 AMPK construct (AMPK α2 KD) in muscles and littermate wildtype (WT) mice were tested. AMPK α2 KD mice have impaired running...... capacity and display reduced voluntary wheel running activity. Striatal content of dopamine and its metabolites were measured under basal physiological conditions and after cocaine-induced dopamine efflux from the ventral striatum by in vivo microdialysis. Moreover, cocaine-induced locomotor activity...

Effects of repeated light-dark phase shifts on voluntary ethanol and water intake in male and female Fischer and Lewis rats.

Science.gov (United States)

Rosenwasser, Alan M; Clark, James W; Fixaris, Michael C; Belanger, Gabriel V; Foster, James A

2010-05-01

Several lines of evidence implicate reciprocal interactions between excessive alcohol (ethanol) intake and dysregulation of circadian biological rhythms. Thus, chronic alcohol intake leads to widespread circadian disruption in both humans and experimental animals, while in turn, chronobiological disruption has been hypothesized to promote or sustain excessive alcohol intake. Nevertheless, the effects of circadian disruption on voluntary ethanol intake have not been investigated extensively, and prior studies have reported both increased and decreased ethanol intake in rats maintained under "shift-lag" lighting regimens mimicking those experienced by shift workers and transmeridian travelers. In the present study, male and female inbred Fischer and Lewis rats were housed in running wheel cages with continuous free-choice access to both water and 10% (vol/vol) ethanol solution and exposed to repeated 6-h phase advances of the daily light-dark (LD) cycle, whereas controls were kept under standard LD 12:12 conditions. Shift-lag lighting reduced overall ethanol and water intake, and reduced ethanol preference in Fischer rats. Although contrary to the hypothesis that circadian disruption would increase voluntary ethanol intake, these results are consistent with our previous report of reduced ethanol intake in selectively bred high-alcohol-drinking (HAD1) rats housed under a similar lighting regimen. We conclude that chronic circadian disruption is a form of chronobiological stressor that, like other stressors, can either increase or decrease ethanol intake, depending on a variety of poorly understood variables. 2010 Elsevier Inc. All rights reserved.

Umbrella Wheel - a stair-climbing and obstacle-handling wheel design concept

DEFF Research Database (Denmark)

Iversen, Simon; Jouffroy, Jerome

2017-01-01

This paper proposes a new design for stair-climbing using a wheel that can split into segments and walk up stairs or surmount other obstacles often found where humans traverse, while still being able to retain a perfectly round shape for traveling on smooth ground. Using this change of configurat......This paper proposes a new design for stair-climbing using a wheel that can split into segments and walk up stairs or surmount other obstacles often found where humans traverse, while still being able to retain a perfectly round shape for traveling on smooth ground. Using this change...... of configuration, staircases with a wide range of dimensions can be covered efficiently and safely. The design, named Umbrella Wheel, can consist of as many wheel segments as desired, and as few as two. A smaller or higher number of wheel segments has advantages and disadvantages depending on the specific...

Wheel running alters patterns of uncontrollable stress-induced cfos mRNA expression in rat dorsal striatum direct and indirect pathways: a possible role for plasticity in adenosine receptors

Science.gov (United States)

Clark, Peter J.; Ghasem, Parsa R.; Mika, Agnieszka; Day, Heidi E.; Herrera, Jonathan J.; Greenwood, Benjamin N.; Fleshner, Monika

2014-01-01

Emerging evidence indicates that adenosine is a major regulator of striatum activity, in part, through the antagonistic modulation of dopaminergic function. Exercise can influence adenosine and dopamine activity, which may subsequently promote plasticity in striatum adenosine and dopamine systems. Such changes could alter activity of medium spiny neurons and impact striatum function. The purpose of this study was two-fold. The first was to characterize the effect of long-term wheel running on adenosine 1 (A1R), adenosine 2A (A2AR), dopamine 1 (D1R), and dopamine 2 (D2R) receptor mRNA expression in adult rat dorsal and ventral striatum structures using in situ hybridization. The second was to determine if changes to adenosine and dopamine receptor mRNA from running are associated with altered cfos mRNA induction in dynorphin- (direct pathway) and enkephalin- (indirect pathway) expressing neurons of the dorsal striatum following stress exposure. We report that chronic running, as well as acute uncontrollable stress, reduced A1R and A2AR mRNA levels in the dorsal and ventral striatum. Running also modestly elevated D2R mRNA levels in striatum regions. Finally, stress-induced cfos was potentiated in dynorphin and attenuated in enkephalin expressing neurons of running rats. These data suggest striatum adenosine and dopamine systems are targets for neuroplasticity from exercise, which may contribute to changes in direct and indirect pathway activity. These findings may have implications for striatum mediated motor and cognitive processes, as well as exercise facilitated stress-resistance. PMID:25017571

Design of Wheeled Mobile Robot with Tri-Star Wheel as Rescue Robot

Directory of Open Access Journals (Sweden)

Rafiuddin Syam

2014-10-01

Full Text Available This study aims to design, and analyze a mobile robot that can handle some of the obstacles, they are uneven surfaces, slopes, can also climb stairs. WMR in this study is Tristar wheel that is containing three wheels for each set. On average surface only two wheels in contact with the surface, if there is an uneven surface or obstacle then the third wheel will rotate with the rotation center of the wheel in contact with the leading obstacle then only one wheel in contact with the surface. This study uses the C language program. Furthermore, the minimum thrust to be generated torque of the motor and transmission is 9.56 kg. The results obtained by calculation and analysis of DC motors used must have a torque greater than 14.67 kg.cm. Minimum thrust to be generated motor torque and the transmission is 9.56 kg. The experimental results give good results for robot to moving forward, backward, turn left, turn right and climbing the stairs.

High frequency vibration characteristics of electric wheel system under in-wheel motor torque ripple

Science.gov (United States)

Mao, Yu; Zuo, Shuguang; Wu, Xudong; Duan, Xianglei

2017-07-01

With the introduction of in-wheel motor, the electric wheel system encounters new vibration problems brought by motor torque ripple excitation. In order to analyze new vibration characteristics of electric wheel system, torque ripple of in-wheel motor based on motor module and vector control system is primarily analyzed, and frequency/order features of the torque ripple are discussed. Then quarter vehicle-electric wheel system (QV-EWS) dynamics model based on the rigid ring tire assumption is established and the main parameters of the model are identified according to tire free modal test. Modal characteristics of the model are further analyzed. The analysis indicates that torque excitation of in-wheel motor is prone to arouse horizontal vibration, in which in-phase rotational, anti-phase rotational and horizontal translational modes of electric wheel system mainly participate. Based on the model, vibration responses of the QV-EWS under torque ripple are simulated. The results show that unlike vertical low frequency (lower than 20 Hz) vibration excited by road roughness, broadband torque ripple will arouse horizontal high frequency (50-100 Hz) vibration of electric wheel system due to participation of the three aforementioned modes. To verify the theoretical analysis, the bench experiment of electric wheel system is conducted and vibration responses are acquired. The experiment demonstrates the high frequency vibration phenomenon of electric wheel system and the measured order features as well as main resonant frequencies agree with simulation results. Through theoretical modeling, analysis and experiments this paper reveals and explains the high frequency vibration characteristics of electric wheel system, providing references for the dynamic analysis, optimal design of QV-EWS.

Eating meals before wheel-running exercise attenuate high fat diet-driven obesity in mice under two meals per day schedule.

Science.gov (United States)

Sasaki, Hiroyuki; Hattori, Yuta; Ikeda, Yuko; Kamagata, Mayo; Shibata, Shigenobu

2015-06-01

Mice that exercise after meals gain less body weight and visceral fat compared to those that exercised before meals under a one meal/exercise time per day schedule. Humans generally eat two or three meals per day, and rarely have only one meal. To extend our previous observations, we examined here whether a "two meals, two exercise sessions per day" schedule was optimal in terms of maintaining a healthy body weight. In this experiment, "morning" refers to the beginning of the active phase (the "morning" for nocturnal animals). We found that 2-h feeding before 2-h exercise in the morning and evening (F-Ex/F-Ex) resulted in greater attenuation of high fat diet (HFD)-induced weight gain compared to other combinations of feeding and exercise under two daily meals and two daily exercise periods. There were no significant differences in total food intake and total wheel counts, but feeding before exercise in the morning groups (F-Ex/F-Ex and F-Ex/Ex-F) increased the morning wheel counts. These results suggest that habitual exercise after feeding in the morning and evening is more effective for preventing HFD-induced weight gain. We also determined whether there were any correlations between food intake, wheel rotation, visceral fat volume and skeletal muscle volumes. We found positive associations between gastrocnemius muscle volumes and morning wheel counts, as well as negative associations between morning food intake volumes/body weight and morning wheel counts. These results suggest that morning exercise-induced increase of muscle volume may refer to anti-obesity. Evening exercise is negatively associated with fat volume increases, suggesting that this practice may counteract fat deposition. Our multifactorial analysis revealed that morning food intake helps to increase exercise, and that evening exercise reduced fat volumes. Thus, exercise in the morning or evening is important for preventing the onset of obesity.

Relationships among the contact patch length and width, the tire deflection and the rolling resistance of a free-running wheel in a soil bin facility

Energy Technology Data Exchange (ETDEWEB)

Tomaraee, P.; Mardani, A.; Mohebbi, A.; Taghavifar, H.

2015-07-01

Qualitative and quantitative analysis of contact patch length-rolling resistance, contact patch width-rolling resistance and tire deflection-rolling resistance at different wheel load and inflation pressure levels is presented. The experiments were planned in a randomized block design and were conducted in the controlled conditions provided by a soil bin environment utilizing a well-equipped single wheel-tester of Urmia University, Iran. The image processing technique was used for determination of the contact patch length and contact patch width. Analysis of covariance was used to evaluate the correlations. The highest values of contact length and width and tire deflection occurred at the highest wheel load and lowest tire inflation pressure. Contact patch width is a polynomial (order 2) function of wheel load while there is a linear relationship between tire contact length and wheel load as well as between tire deflection and wheel load. Correlations were developed for the evaluation of contact patch length-rolling resistance, contact patch width-rolling resistance and tire deflection-rolling resistance. It is concluded that the variables studied have a significant effect on rolling resistance. (Author)

Development of dynamic models of wagons on models 18-9810 and 18-9855 bogies taking into account wheel wear research

Directory of Open Access Journals (Sweden)

A. V. Saidova

2013-04-01

Full Text Available Purpose. Wear parameters clarification in wear simulation is an actual goal because of absence of corresponding data for freight cars in condition of using them on Russian railways. Research is devoted to development of dynamic models of wagons on three-peace two-axle models 18-9810 and 18-9855 bogies with maximum axle-loads 23,5 ts and 25 ts, and to choice of factors, with varying which parameters in the model of wheel wear can be identified. Methodology. The problem is solved by method of mathematic simulation in «MEDYNA» software. Wear calculation is based on abrasive wear theory (Archard’s theory. Findings. Clarification of wheels’ wear model may be done with varying of friction coefficient between wheel and rail for different wheel profile areas (flange and tread, wear coefficient in Archard’s model for mild and heavy wear and transition between them. Originality. Dynamic models of universal gondola on models 18-9810 and 18-9855 bogies are developed. It is established, that rail treads irregularities size effect wheel wear insignificantly, when car is running on circle track of constant radius. Practical value. Developed dynamic models of wagons on models 18-9810 and 18-9855 bogies may be used in wear simulation, determination of car running characteristics, interaction of car and rail of different type, construction, condition and etc. Research results of some factors influence on freight car wheel wear may be interesting for people, who study this problem.

Time-domain simulation and nonlinear analysis on ride performance of four-wheel vehicles

Energy Technology Data Exchange (ETDEWEB)

Wang, Y S; He, H; Geng, A L [School of Automobile and Traffic Engineering, Liaoning University of Technology, Jinzhou 121001 (China)], E-mail: jzwbt@163.com

2008-02-15

A nonlinear dynamic model with eight DOFs of a four-wheel vehicle is established in this paper. After detaching the nonlinear characteristics of the leaf springs and shock absorbers, the multi-step linearizing method is used to simulate the vehicle vibration in time domain, under a correlated four-wheel road roughness model. Experimental verifications suggest that the newly built vehicle model and simulation procedure are reasonable and feasible to be used in vehicle vibration analysis. Furthermore, some nonlinear factors of the leaf springs and shock absorbers, which affect the vehicle ride performance (or comfort), are investigated under different vehicle running speeds. Some substaintial rules of the nonlinear vehicle vibrations are revealed in this paper.

Time-domain simulation and nonlinear analysis on ride performance of four-wheel vehicles

International Nuclear Information System (INIS)

Wang, Y S; He, H; Geng, A L

2008-01-01

A nonlinear dynamic model with eight DOFs of a four-wheel vehicle is established in this paper. After detaching the nonlinear characteristics of the leaf springs and shock absorbers, the multi-step linearizing method is used to simulate the vehicle vibration in time domain, under a correlated four-wheel road roughness model. Experimental verifications suggest that the newly built vehicle model and simulation procedure are reasonable and feasible to be used in vehicle vibration analysis. Furthermore, some nonlinear factors of the leaf springs and shock absorbers, which affect the vehicle ride performance (or comfort), are investigated under different vehicle running speeds. Some substaintial rules of the nonlinear vehicle vibrations are revealed in this paper

Circadian activity rhythms and voluntary ethanol intake in male and female ethanol-preferring rats: effects of long-term ethanol access.

Science.gov (United States)

Rosenwasser, Alan M; McCulley, Walter D; Fecteau, Matthew

2014-11-01

Chronic alcohol (ethanol) intake alters fundamental properties of the circadian clock. While previous studies have reported significant alterations in free-running circadian period during chronic ethanol access, these effects are typically subtle and appear to require high levels of intake. In the present study we examined the effects of long-term voluntary ethanol intake on ethanol consumption and free-running circadian period in male and female, selectively bred ethanol-preferring P and HAD2 rats. In light of previous reports that intermittent access can result in escalated ethanol intake, an initial 2-week water-only baseline was followed by either continuous or intermittent ethanol access (i.e., alternating 15-day epochs of ethanol access and ethanol deprivation) in separate groups of rats. Thus, animals were exposed to either 135 days of continuous ethanol access or to five 15-day access periods alternating with four 15-day periods of ethanol deprivation. Animals were maintained individually in running-wheel cages under continuous darkness throughout the experiment to allow monitoring of free-running activity and drinking rhythms, and 10% (v/v) ethanol and plain water were available continuously via separate drinking tubes during ethanol access. While there were no initial sex differences in ethanol drinking, ethanol preference increased progressively in male P and HAD2 rats under both continuous and intermittent-access conditions, and eventually exceeded that seen in females. Free-running period shortened during the initial ethanol-access epoch in all groups, but the persistence of this effect showed complex dependence on sex, breeding line, and ethanol-access schedule. Finally, while females of both breeding lines displayed higher levels of locomotor activity than males, there was little evidence for modulation of activity level by ethanol access. These results are consistent with previous findings that chronic ethanol intake alters free-running circadian

A dynamic wheel-rail impact analysis of railway track under wheel flat by finite element analysis

Science.gov (United States)

Bian, Jian; Gu, Yuantong; Murray, Martin Howard

2013-06-01

Wheel-rail interaction is one of the most important research topics in railway engineering. It involves track impact response, track vibration and track safety. Track structure failures caused by wheel-rail impact forces can lead to significant economic loss for track owners through damage to rails and to the sleepers beneath. Wheel-rail impact forces occur because of imperfections in the wheels or rails such as wheel flats, irregular wheel profiles, rail corrugations and differences in the heights of rails connected at a welded joint. A wheel flat can cause a large dynamic impact force as well as a forced vibration with a high frequency, which can cause damage to the track structure. In the present work, a three-dimensional finite element (FE) model for the impact analysis induced by the wheel flat is developed by the use of the FE analysis (FEA) software package ANSYS and validated by another validated simulation. The effect of wheel flats on impact forces is thoroughly investigated. It is found that the presence of a wheel flat will significantly increase the dynamic impact force on both rail and sleeper. The impact force will monotonically increase with the size of wheel flats. The relationships between the impact force and the wheel flat size are explored from this FEA and they are important for track engineers to improve their understanding of the design and maintenance of the track system.

The Influence of Wheel/Rail Contact Conditions on the Microstructure and Hardness of Railway Wheels

Directory of Open Access Journals (Sweden)

Paul Molyneux-Berry

2014-01-01

Full Text Available The susceptibility of railway wheels to wear and rolling contact fatigue damage is influenced by the properties of the wheel material. These are influenced by the steel composition, wheel manufacturing process, and thermal and mechanical loading during operation. The in-service properties therefore vary with depth below the surface and with position across the wheel tread. This paper discusses the stress history at the wheel/rail contact (derived from dynamic simulations and observed variations in hardness and microstructure. It is shown that the hardness of an “in-service” wheel rim varies significantly, with three distinct effects. The underlying hardness trend with depth can be related to microstructural changes during manufacturing (proeutectoid ferrite fraction and pearlite lamellae spacing. The near-surface layer exhibits plastic flow and microstructural shear, especially in regions which experience high tangential forces when curving, with consequentially higher hardness values. Between 1 mm and 7 mm depth, the wheel/rail contacts cause stresses exceeding the material yield stress, leading to work hardening, without a macroscopic change in microstructure. These changes in material properties through the depth of the wheel rim would tend to increase the likelihood of crack initiation on wheels toward the end of their life. This correlates with observations from several train fleets.

49 CFR 570.10 - Wheel assemblies.

Science.gov (United States)

2010-10-01

... bead through one full wheel revolution and note runout in excess of one-eighth of an inch. (c) Mounting... 49 Transportation 6 2010-10-01 2010-10-01 false Wheel assemblies. 570.10 Section 570.10... Pounds or Less § 570.10 Wheel assemblies. (a) Wheel integrity. A tire rim, wheel disc, or spider shall...

Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

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Xianglong eZhu

2016-04-01

Full Text Available While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running. The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control.

Design of Wheeled Mobile Robot with Tri-Star Wheel as Rescue Robot

Directory of Open Access Journals (Sweden)

Rafiuddin Syam

2016-05-01

Full Text Available This study aims to design, and analyze a mobilerobot that can handle some of the obstacles, they are unevensurfaces, slopes, can also climb stairs. WMR in this study is Tristarwheel that is containing three wheels for each set. Onaverage surface only two wheels in contact with the surface, ifthere is an uneven surface or obstacle then the third wheel willrotate with the rotation center of the wheel in contact with theleading obstacle then only one wheel in contact with the surface.This study uses the C language program. Furthermore, theminimum thrust to be generated torque of the motor andtransmission is 9.56 kg. The results obtained by calculation andanalysis of DC motors used must have a torque greater than14.67 kg.cm. Minimum thrust to be generated motor torque andthe transmission is 9.56 kg. The experimental results give goodresults for robot to moving forward, backward, turn left, turnright and climbing the stairs

Using unconstrained tongue motion as an alternative control mechanism for wheeled mobility.

Science.gov (United States)

Huo, Xueliang; Ghovanloo, Maysam

2009-06-01

Tongue drive system (TDS) is a tongue-operated, minimally invasive, unobtrusive, noncontact, and wireless assistive technology that infers users' intentions by detecting and classifying their voluntary tongue motions, and translating them to user-defined commands. We have developed customized interface circuitry between an external TDS (eTDS) prototype and a commercial powered wheelchair (PWC) as well as three control strategies to evaluate the tongue motion as an alternative control input for wheeled mobility. We tested the eTDS performance in driving PWCs on 12 able-bodied human subjects, of which 11 were novice. The results showed that all subjects could complete navigation tasks by operating the PWC using their tongue motions. Despite little prior experience, the average time using the eTDS and the tongue was only approximately three times longer than using a joystick and the fingers. Navigation time was strongly dependant on the number of issued commands, which reduced by gaining experience. Particularly, the unintended issued commands (the Midas touch problem) were rare, demonstrating the effectiveness of the tongue tracking and external magnetic field cancellation algorithms as well as the safety of the TDS for wheeled mobility.

Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers

Science.gov (United States)

Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

2017-01-01

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can attenuate the severity of colonic damage in mice fed a HFD through the release of protective irisin and restoration of plasma adiponectin. PMID:28425943

Numerical Analysis of Partial Abrasion of the Straddle-type Monorail Vehicle running Tyre

OpenAIRE

Du, Zixue; Wen, Xiaoxia; Zhao, Dayi; Xu, Zhouzhou; Chen, Liang

2017-01-01

The finite element model of the running tyre and the pre-stressed concrete (PC) track beam are created in the study. The wheel-rail contact status under the conditions such as acceleration or braking, lateral deviation, and roll is analysed. The wear law of the running tyre under the operating condition of driving on winding roads is discussed. The results show that the running tyre will unevenly wear when driving on the winding road; the smaller curve radius and the faster speed result in he...

Wheeled mobility device transportation safety in fixed route and demand-responsive public transit vehicles within the United States.

Science.gov (United States)

Frost, Karen L; van Roosmalen, Linda; Bertocci, Gina; Cross, Douglas J

2012-01-01

An overview of the current status of wheelchair transportation safety in fixed route and demand-responsive, non-rail, public transportation vehicles within the US is presented. A description of each mode of transportation is provided, followed by a discussion of the primary issues affecting safety, accessibility, and usability. Technologies such as lifts, ramps, securement systems, and occupant restraint systems, along with regulations and voluntary industry standards have been implemented with the intent of improving safety and accessibility for individuals who travel while seated in their wheeled mobility device (e.g., wheelchair or scooter). However, across both fixed route and demand-responsive transit systems a myriad of factors such as nonuse and misuse of safety systems, oversized wheeled mobility devices, vehicle space constraints, and inadequate vehicle operator training may place wheeled mobility device (WhMD) users at risk of injury even under non-impact driving conditions. Since WhMD-related incidents also often occur during the boarding and alighting process, the frequency of these events, along with factors associated with these events are described for each transit mode. Recommendations for improving WhMD transportation are discussed given the current state of

Electron Beam Welding of Gear Wheels by Splitted Beam

Directory of Open Access Journals (Sweden)

Dřímal Daniel

2014-06-01

Full Text Available This contribution deals with the issue of electron beam welding of high-accurate gear wheels composed of a spur gearing and fluted shaft joined with a face weld for automotive industry. Both parts made of the high-strength low-alloy steel are welded in the condition after final machining and heat treatment, performed by case hardening, whereas it is required that the run-out in the critical point of weldment after welding, i. e. after the final operation, would be 0.04 mm max..

Regularities of shaping of a wheel profile as a result of deterioration of the rolling surface in exploitation

Directory of Open Access Journals (Sweden)

Aleksander VORON’KO

2008-01-01

Full Text Available In the middle of the 90s the deterioration of wheels flanges and lateral rail surfaces on roads in the countries of CIS from natural process of wear process of surfaces has turned to the sharp problem which has received the status of a «rail plague». On separate roads the lateral deterioration of rails has reached 1 mm times 106 tons, by exceeding a level of normative deterioration in some times. Thus the run of wheel pairs between regrinding on flange undercuts was reduced in by 3-5 times [5]. In the article some ways of elimination of deterioration of wheels and rails are considered. The technique of process modeling of parameters changes of deterioration is offered.

INFLUENCE OF USUAL AND DUAL WHEELS ON SOIL PENETRATION RESISTANCE: THE GIS-APPROACH

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Zhukov A. V.

2015-12-01

Full Text Available GIS-APPROACH application has allowed establishing that usual wheels of machine-tractor units carry out considerable influence on soil which exceeds visible borders of a track of wheels on the dimensions. This influence shows in augmentation of soil penetration resistance at 100-155 % in comparison with the control on depth of 0-10 cm and on 20-30 % on depth of 45-50 %. It is impossible to exclude that influence of wheels proceeds more deeply, than tests have been conducted. Critical for cultivated plants value of soil penetration resistance in 3 MPa under the influence of usual wheels of agricultural machinery comes nearer practically to a surface. Character of profile changes of hardness in various regions influences of wheels allows assuming the long season of a relaxation of soil for achievement of background values of soil penetration resistance. The further researches are necessary for an establishment of concrete indicators of dynamics. Negative influence of an overstocking does not confine only deterioration of conditions of growth of assemblages of rootlets of plants. Infringement of processes of moving of moisture in the soil, the accelerated evaporation and the slowed down processes of a filtration and an infiltration, destruction of modular frame, activization of erosive processes is possible. The understanding of these processes will give the chance volume understanding of real influence of running systems of machine-tractor devices on bedrock. Region intensive influence of dual wheels is circumscribed by the top soil layers (0-15 cm. The major feature of influence of dual wheels is absence of an overstocking above critical levels. It is impossible to exclude possible positive influence of moderate inspissations of soil under the influence of dual wheels for growth of agricultural crops and moisture conservation in soil. The cumulative negative effect on soil crossed vehicles traces is probable. The long season of a relaxation of

Development of self-running underwater cleaner for nuclear facilities

International Nuclear Information System (INIS)

Ito, Haruo; Mizutani, Takeshi; Miki, Masamichi

1979-01-01

A self-running underwater cleaner for removing sediment accumulated on the bottoms of water tanks in nuclear power stations by remote operation was developed. This cleaner is used in the state maintaining the shielding effect of water against radiation as water is filled in equipment pits, and by the remote operation using cables, it runs freely in water and sucks bottom sediment. The sediment is transported through a drain hose to a treating facility in a power station, and treated in a lump. The cleaner is composed of the carriage with electric steering wheels and driving wheels and a high head submerged pump. Front and rear suction mouths are provided, and suck sediment with high speed water flow while scraping with rubber boards. The cleaner can be used in the water depth of 7 m, and as the results of practical test, it was confirmed that the decontaminating effect and maneuverability were very good so that the sediment at the corner was scarcely left behind, and the effects of labor saving and the reduction of exposure of employees were large. The fundamental experiments were carried out on the running mechanism, the coefficient of friction in water, and the construction of suction mouth. The trial manufacture of the under water cleaner, the water tank experiment and the test in the Mamaoka No. 1 plant are reported. (Kako, I.)

New methodology for fast prediction of wheel wear evolution

Science.gov (United States)

Apezetxea, I. S.; Perez, X.; Casanueva, C.; Alonso, A.

2017-07-01

In railway applications wear prediction in the wheel-rail interface is a fundamental matter in order to study problems such as wheel lifespan and the evolution of vehicle dynamic characteristic with time. However, one of the principal drawbacks of the existing methodologies for calculating the wear evolution is the computational cost. This paper proposes a new wear prediction methodology with a reduced computational cost. This methodology is based on two main steps: the first one is the substitution of the calculations over the whole network by the calculation of the contact conditions in certain characteristic point from whose result the wheel wear evolution can be inferred. The second one is the substitution of the dynamic calculation (time integration calculations) by the quasi-static calculation (the solution of the quasi-static situation of a vehicle at a certain point which is the same that neglecting the acceleration terms in the dynamic equations). These simplifications allow a significant reduction of computational cost to be obtained while maintaining an acceptable level of accuracy (error order of 5-10%). Several case studies are analysed along the paper with the objective of assessing the proposed methodology. The results obtained in the case studies allow concluding that the proposed methodology is valid for an arbitrary vehicle running through an arbitrary track layout.

Grinding Characteristics Of Directionally Aligned SiC Whisker Wheel-Comparison With Al2O3 Fiber Wheel

Institute of Scientific and Technical Information of China (English)

魏源迁; 山口胜美; 菊泽贤二; 洞口严; 中根正喜

2003-01-01

A unique SiC whisker wheel was invented,in which the whiskers were aligned normally to the grinding wheel surface.In this paper,grindabilities of the SiC whisker wheel are investigated and compared with those of other wheels of SiC grains,Al2O3 grains,as well as Al2O3 long and short fibres which were also aligned normally to the grinding wheel surface,respectively.The main research contents concern grinding characteristics of a directionally aligned SiC whisker wheel such as material-removal volume,wheel-wear rates,integrity of the ground surfaces,grinding ratios and grinding efficiency.Furthermore,grinding wheels of whiskers and fibres have a common disadvantage:they tend to load easily.The authors have proposed a simple method of loading-free grinding to overcome this propensity and investigate some related grinding characteristics under loading-free grinding conditions.

Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity.

Science.gov (United States)

Schroeder, Mariana; Shbiro, Liat; Gelber, Vered; Weller, Aron

2010-04-01

Given the alarming increase in childhood, adolescent and adult obesity there is an imperative need for understanding the early factors affecting obesity and for treatments that may help prevent or at least moderate it. Exercise is frequently considered as an effective treatment for obesity however the empirical literature includes many conflicting findings. In the present study, we used the OLETF rat model of early-onset hyperphagia-induced obesity to examine the influence of early exercise on peripheral adiposity-related parameters in both males and females. Rats were provided voluntary access to running wheels from postnatal day (PND) 22 until PND45. We examined fat pad weight (brown, retroperitoneal, inguinal and epididymal); inguinal adipocyte size and number; and leptin, adiponectin, corticosterone and creatinine levels. We also examined body weight, feeding efficiency and spontaneous intake. Early voluntary exercise reduced intake, adiposity and leptin in the OLETF males following a sharp reduction in adipocyte size despite a significant increase in fat cell number. Exercising males from the lean LETO control strain presented stable intake, but reduced body fat, feeding efficiency and increased plasma creatinine, suggesting an increment in muscle mass. OLETF females showed reduced feeding efficiency and liver fat, and a significant increase in brown fat. Exercising LETO control females increased intake, body weight and creatinine, but no changes in body fat. Overall, OLETF rats presented higher adiponectin levels than controls in both basal and post-exercise conditions. The results suggest an effective early time frame, when OLETF males can be successfully "re-programmed" through voluntary exercise; in OLETF females the effect is much more moderate. Findings expose sex-dependent peripheral mechanisms in coping with energy challenges. Copyright 2010 Elsevier Inc. All rights reserved.

Tracked Vehicle Road Wheel Puller

Science.gov (United States)

2009-02-01

employed for removing smaller-size components, such as bolts and the like. U.S. Patent No. 5,410,792, issued to Freeman (3), discloses a caster wheel ...separation of the rubberized annular layer from the outer annular surface of the wheel . Figure 5 further illustrates a modification of the wheel puller...2001. 2. Rubino et al. Pulling Tool. U.S. Patent 5,479,688, 1996. 3. Freeman. Caster Wheel Axle Extraction Apparatus. U.S. Patent 5,410,792

Sieving for pseudosquares and pseudocubes in parallel using doubly-focused enumeration and wheel datastructures

OpenAIRE

Sorenson, Jonathan P.

2010-01-01

We extend the known tables of pseudosquares and pseudocubes, discuss the implications of these new data on the conjectured distribution of pseudosquares and pseudocubes, and present the details of the algorithm used to do this work. Our algorithm is based on the space-saving wheel data structure combined with doubly-focused enumeration, run in parallel on a cluster supercomputer.

Methamphetamine blocks exercise effects on Bdnf and Drd2 gene expression in frontal cortex and striatum.

Science.gov (United States)

Thompson, Andrew B; Stolyarova, Alexandra; Ying, Zhe; Zhuang, Yumei; Gómez-Pinilla, Fernando; Izquierdo, Alicia

2015-12-01

Exposure to drugs of abuse can produce many neurobiological changes which may lead to increased valuation of rewards and decreased sensitivity to their costs. Many of these behavioral alterations are associated with activity of D2-expressing medium spiny neurons in the striatum. Additionally, Bdnf in the striatum has been shown to play a role in flexible reward-seeking behavior. Given that voluntary aerobic exercise can affect the expression of these proteins in healthy subjects, and that exercise has shown promise as an anti-addictive therapy, we set out to quantify changes in D2 and Bdnf expression in methamphetamine-exposed rats given access to running wheels. Sixty-four rats were treated for two weeks with an escalating dose of methamphetamine or saline, then either sacrificed, housed in standard cages, or given free access to a running wheel for 6 weeks prior to sacrifice. Rats treated with methamphetamine ran significantly greater distances than saline-treated rats, suggesting an augmentation in the reinforcement value of voluntary wheel running. Transcription of Drd2 and Bdnf was assessed via RT-qPCR. Protein expression levels of D2 and phosphorylation of the TrkB receptor were measured via western blot. Drd2 and Bdnf mRNA levels were impacted independently by exercise and methamphetamine, but exposure to methamphetamine prior to the initiation of exercise blocked the exercise-induced changes seen in rats treated with saline. Expression levels of both proteins were elevated immediately after methamphetamine, but returned to baseline after six weeks, regardless of exercise status. Copyright © 2015 Elsevier Ltd. All rights reserved.

Grinding Wheel System

Science.gov (United States)

Malkin, Stephen; Gao, Robert; Guo, Changsheng; Varghese, Biju; Pathare, Sumukh

2003-08-05

A grinding wheel system includes a grinding wheel with at least one embedded sensor. The system also includes an adapter disk containing electronics that process signals produced by each embedded sensor and that transmits sensor information to a data processing platform for further processing of the transmitted information.

Recovery tread wheel pairs of machining

Directory of Open Access Journals (Sweden)

Igor IVANOV

2013-01-01

Full Text Available The basic methods of resurfacing wheels are determined and analised. It’sshown that for raising resource of used wheels and decreasing requirements of railwaytransport for new wheels it’s reasonable to use methods of recovering not only geometricparameters of rim, but also its mechanical properties. It’s marked that use of infeedprofile high-speed grinding (VPVSh enables to intensify significantly process ofmechanical treatment of wheel rim profile both when its resurfacing in service and whenmanufacturing new wheel.

Wheeling in Canada

International Nuclear Information System (INIS)

Fytche, E.L.

1991-01-01

The quest for economic efficiency, or lowest cost, in the electricity supply industry is furthered by trading between high and low cost utilities, one aspect being transporting or wheeling power through the transmission system of a third party. Some of the pressures and constraints limiting wheeling are discussed. A simple formula is presented for determining whether trading and wheeling are worthwhile. It is demonstrated for assumed capital and operating cost levels, the viability of nine cases where bulk power or economy energy would need to be wheeled across provincial boundaries in order to reach potential buyers. Wheeling in Canada is different from the situation in the USA, due to large distances spanned by Canadian utilities and because most are provincial crown corporations, with different territorial interests and profit motivations than investor-owned utilities. Most trading in electricity has been between contiguous neighbours, for mutual advantage. New technology allows power transmission over distances of up to 1000 miles, and the economics of Canada's electrical supply could be improved, with means including access to low cost coal of Alberta, and remote hydro in British Columbia, Manitoba, Quebec and Labrador. Nuclear plants could be located anywhere but suffer from an unfriendly public attitude. A bridge across the Prairies appears uneconomic due to cost of transmission, and also due to low valuation given to Alberta coal. 7 refs., 2 figs., 3 tabs

The hydraulic wheel

International Nuclear Information System (INIS)

Alvarez Cardona, A.

1985-01-01

The present article this dedicated to recover a technology that key in disuse for the appearance of other techniques. It is the hydraulic wheel with their multiple possibilities to use their energy mechanical rotational in direct form or to generate electricity directly in the fields in the place and to avoid the high cost of transport and transformation. The basic theory is described that consists in: the power of the currents of water and the hydraulic receivers. The power of the currents is determined knowing the flow and east knowing the section of the flow and its speed; they are given you formulate to know these and direct mensuration methods by means of floodgates, drains and jumps of water. The hydraulic receivers or properly this hydraulic wheels that are the machines in those that the water acts like main force and they are designed to transmit the biggest proportion possible of absolute work of the water, the hydraulic wheels of horizontal axis are the common and they are divided in: you rotate with water for under, you rotate with side water and wheels with water for above. It is analyzed each one of them, their components are described; the conditions that should complete to produce a certain power and formulate them to calculate it. There are 25 descriptive figures of the different hydraulic wheels

Wheel speed management control system for spacecraft

Science.gov (United States)

Goodzeit, Neil E. (Inventor); Linder, David M. (Inventor)

1991-01-01

A spacecraft attitude control system uses at least four reaction wheels. In order to minimize reaction wheel speed and therefore power, a wheel speed management system is provided. The management system monitors the wheel speeds and generates a wheel speed error vector. The error vector is integrated, and the error vector and its integral are combined to form a correction vector. The correction vector is summed with the attitude control torque command signals for driving the reaction wheels.

Voluntary physical exercise alters attentional orienting and social behavior in a rat model of attention-deficit/hyperactivity disorder.

Science.gov (United States)

Hopkins, Michael E; Sharma, Mita; Evans, Gretchen C; Bucci, David J

2009-06-01

The effects of voluntary physical exercise on attentional function and social behavior were examined in male and female spontaneously hypertensive rats (SHR), a commonly used animal model of attention-deficit/hyperactivity disorder (ADHD). Rats in the exercise groups had free access to a running wheel for 2 weeks and then all rats received nonreinforced presentations of a visual stimulus (light) during the 1st training session, followed by daily sessions in which the light was paired with food. Nonexercising male and female SHR rats exhibited more unconditioned orienting behavior than Wistar-Kyoto rats. SHRs also exhibited impaired conditioning when the light was paired with food. Exercise reduced orienting in female SHRs but not in male SHRs. In the social interaction task, nonexercising male and female SHRs interacted more with an unfamiliar rat than Wistar-Kyoto rats. Exercise reduced the number of social interactions in female SHRs but not male SHRs. There were no differences in general locomotor activity observed between the nonexercising and exercising SHRs. These data indicate that exercise may preferentially benefit female SHRs, and has implications for using exercise as an intervention for ADHD and for understanding sex differences in the effects of exercise on behavior. Copyright (c) 2009 APA, all rights reserved.

MATHEMATICAL MODEL OF WHEELSET OSCILLATIONS WITH INDEPENDENT WHEEL ROTATION IN THE HORIZONTAL PLANE

Directory of Open Access Journals (Sweden)

S. V. Myamlin

2016-08-01

wheel rotation. Practical value. The developed mathematical model of the single wheelset motion with independent wheel rotation can be used to create the advanced designs of railway running gear of cars.

Running Improves Pattern Separation during Novel Object Recognition.

Science.gov (United States)

Bolz, Leoni; Heigele, Stefanie; Bischofberger, Josef

2015-10-09

Running increases adult neurogenesis and improves pattern separation in various memory tasks including context fear conditioning or touch-screen based spatial learning. However, it is unknown whether pattern separation is improved in spontaneous behavior, not emotionally biased by positive or negative reinforcement. Here we investigated the effect of voluntary running on pattern separation during novel object recognition in mice using relatively similar or substantially different objects.We show that running increases hippocampal neurogenesis but does not affect object recognition memory with 1.5 h delay after sample phase. By contrast, at 24 h delay, running significantly improves recognition memory for similar objects, whereas highly different objects can be distinguished by both, running and sedentary mice. These data show that physical exercise improves pattern separation, independent of negative or positive reinforcement. In sedentary mice there is a pronounced temporal gradient for remembering object details. In running mice, however, increased neurogenesis improves hippocampal coding and temporally preserves distinction of novel objects from familiar ones.

Wheel inspection system environment.

Science.gov (United States)

2008-11-18

International Electronic Machines Corporation (IEM) has developed and is now marketing a state-of-the-art Wheel Inspection System Environment (WISE). WISE provides wheel profile and dimensional measurements, i.e. rim thickness, flange height, flange ...

The prospects for retail wheeling

International Nuclear Information System (INIS)

O'Donnell, E.H.; Center, J.A.

1992-01-01

This paper as published is an outline of a presentation on retail wheeling of electric power. The topics discussed are development of increased wholesale transmission access, government regulatory policies on wholesale transmission, examples of past and present retail transmission access agreements, examples of Federal Energy Regulatory Commission jurisdiction over retail wheeling, and state policies on retail wheeling

Four-Wheel Vehicle Suspension System

Science.gov (United States)

Bickler, Donald B.

1990-01-01

Four-wheel suspension system uses simple system of levers with no compliant components to provide three-point suspension of chassis of vehicle while maintaining four-point contact with uneven terrain. Provides stability against tipping of four-point rectangular base, without rocking contact to which rigid four-wheel frame susceptible. Similar to six-wheel suspension system described in "Articulated Suspension Without Springs" (NPO-17354).

Assessing the influence of wheel defects of a rolling stockon railway tracks

Directory of Open Access Journals (Sweden)

Loktev Aleksey Alekseevich

2015-05-01

Full Text Available Transfer of the load from the wheels on the rail occurs at a very small area compared with the size of the wheels and rails. The materials near this site have a very large voltage. Determination of contact stresses is complicated by the fact that the magnitude of these stresses in the rails under actually revolving wheel load exceeds the yield and compressive strength of modern rail steel. We should note that the metal of the rail head, experiencing contact stresses, especially when the location of the pads is closer to the middle of the rail head, works in the conditions close to the compression conditions, and therefore can withstand higher voltage without plastic deformation than the standard compressible sample. But, as a rule, the observed hardening of the metal in the zone of contact stresses and lapping at the edges of the rail head indicates the presence of plastic deformation and, consequently, higher stresses in the wheel-rail contact zone than the yield strength of the metal rail even in the conditions of its operation in the rail head.The use of the design equations derived on the basis of the Hertz theory for metal behavior in elastic stage, is valid. The reason is that each individual dynamic application of wheel loads on the rail is very short, and the residual plastic deformation from the individual loads of the pair of wheels on the rail is actually small. This elastic-plastic deformation of the rail becomes visible as a result of gradual gaining of a missed tonnage of rails and wheels respectively. Irregularities on the running surface of the wheels are of two types. The most common are the so-called continuous bumps on the wheel, when due to the uneven wear of rail the original shape of the wheel across the tread surface distorts. But nowadays, more and more often there occur isolated smooth irregularities of the wheel pairs, due to the increased wear of the wheel because of the stopping and blocking of wheels of the vehicles

The Reaction Wheel Pendulum

CERN Document Server

Block, Daniel J; Spong, Mark W

2007-01-01

This monograph describes the Reaction Wheel Pendulum, the newest inverted-pendulum-like device for control education and research. We discuss the history and background of the reaction wheel pendulum and other similar experimental devices. We develop mathematical models of the reaction wheel pendulum in depth, including linear and nonlinear models, and models of the sensors and actuators that are used for feedback control. We treat various aspects of the control problem, from linear control of themotor, to stabilization of the pendulum about an equilibrium configuration using linear control, t

Propulsion Wheel Motor for an Electric Vehicle

Science.gov (United States)

Figuered, Joshua M. (Inventor); Herrera, Eduardo (Inventor); Waligora, Thomas M. (Inventor); Bluethmann, William J. (Inventor); Farrell, Logan Christopher (Inventor); Lee, Chunhao J. (Inventor); Vitale, Robert L. (Inventor); Winn, Ross Briant (Inventor); Eggleston, IV, Raymond Edward (Inventor); Guo, Raymond (Inventor);

Effects of the stress field induced by a running tyre on the soil pore system

DEFF Research Database (Denmark)

Berisso, Feto Esimo; Schjønning, Per; Lamandé, Mathieu

2013-01-01

state in the soil profile beneath the harvester tyre was calculated using the SoilFlex model. Pore continuity index (N) and blocked air-filled porosity (εb) were estimated from the relationship between ka and air-filled porosity (εa) for a range of matric potentials. Calculated and measured stresses...... repeated wheelings were performed by a forage harvester (wheel load 6100 kg; tyre width 80 cm). Mean normal and horizontal stresses were measured with Bolling probes (at 10, 20 and 40 cm depth) and load cells (at 40, 50, 60 cm lateral distance from the centreline of the wheel rut at 10, 30 and 50 cm depth......), respectively. Intact soil cores of 100 cm3 sampled at 10, 30 and 50 cm depth in a soil transcet running from the centreline of the wheel rut to the unwheeled part of the field were used for measurements of water retention and air permeability (ka) at −30, −100 and −300 hPa matric potential. The complete stress...

Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery in Mice

Science.gov (United States)

2012-09-01

the most humane and scientifically rigid because it eliminates the need for stressful procedures (for example, han- dling, restraint) yet...techn1que. Each transmitter was disinfected by presoaking for 5 h in cold sterilant (Actril, Minntech, Minneapolis, MN) followed by multiple rinses in 0.9...Ethicon, Somerville, NJ). The peritoneal muscle layer (5-0 Vic- ryl, Ethicon) and skin (5-0 plain gut , Ethicon) were closed with absorbable sutures

Voluntary euthanasia.

Science.gov (United States)

Brewin, Thurstan B

1986-05-10

Brewin comments upon James Rachels' The End of Life (Oxford University Press; 1986) and Voluntary Euthanasia (Peter Owen; 1986), a compilation edited by A.B. Downing and B. Smoker that is an expanded version of a 1969 work by Britain's Voluntary Euthanasia Society. Rachels maintains that it is illogical to distinguish between active and passive euthanasia. In Voluntary Euthanasia, 17 contributors argue the pros and cons of the issue. The Voluntary Euthanasia Society proposes that mentally competent persons be allowed by law to request euthanasia, either when taken ill or by advance directive. Brewin says he is almost but not quite convinced by the arguments for legalized voluntary euthanasia. He is concerned about the "slippery slope," the uncertainties of prognosis and quality of life judgments, the pressures to which the terminally ill or aged might be subjected, and the potentially negative impact of euthanasia on the physician patient relationship.

Biaxial wheel/hub test facility. Proceedings

Energy Technology Data Exchange (ETDEWEB)

Fischer, G.; Grubisic, V. [eds.

2000-07-01

The 4{sup th} meeting aims to exchange the experience and knowledge of engineers during several presentations and discussions about new developments required for a reliable, time and cost reducing validation of the wheel/hub assembly. Tremendous development of the wheel performance, described by the ratio of the rated load (kg) versus the wheel weight (kg) had taken place during the last 5000 years. Starting from the ratio of 3 for wooden 2-piece-disc-wheels in Mesopotamia it needed nearly 1000 years to increase the ratio to approx 5 at light-weight spoke wheels for fighting carriages, found in the grave of king Tutenchamon in Egypt. Modern light alloy wheels of commercial vehicles reach values up to 160 kg/kg. Additionally the comlex design of the modern systems for cars and commercial vehicles comprising wheel, brake, hub, bearing, spindle and hub carrier, including different materials and their treatment, fasteners, press-fits, require an appropriate testing procedure. The variable loading conditions, caused by operational wheel forces, brake and torque moments including heating, may result in changing tolerances and press-fits during operation and consequently in different damage mechanisms. This can be simulated in the Biaxial Wheel Test Machine, whereby corresponding load programs are necessary. An overview about all biaxial test machines in usage at the end of 1999 is shown in the introduction. The total number is 17 for cars, 7 for commercial vehicles and 1 for trains. The six presentations of this meeting were consequently concentrated on: (a) recommendations for a standardization of load programs of the German Wheel Committee, (b) the simulation of brake and torque events and (c) the possibility for a numerical stress analyses and fatigue life assessment. (orig./AKF)

A Nontoxic Barlow's Wheel

Science.gov (United States)

Daffron, John A.; Greenslade, Thomas B.

2015-01-01

Barlow's wheel has been a favorite demonstration since its invention by Peter Barlow (1776-1862) in 1822.1 In the form shown in Fig. 1, it represents the first electric motor. The interaction between the electric current passing from the axle of the wheel to the rim and the magnetic field produced by the U-magnet produces a torque that turns the wheel. The original device used mercury to provide electrical contact to the rim, and the dangers involved with the use of this heavy metal have caused the apparatus to disappear from the lecture hall.

Reaction wheels for kinetic energy storage

Science.gov (United States)

Studer, P. A.

1984-11-01

In contrast to all existing reaction wheel implementations, an order of magnitude increase in speed can be obtained efficiently if power to the actuators can be recovered. This allows a combined attitude control-energy storage system to be developed with structure mounted reaction wheels. The feasibility of combining reaction wheels with energy storage wwheels is demonstrated. The power required for control torques is a function of wheel speed but this energy is not dissipated; it is stored in the wheel. The I(2)R loss resulting from a given torque is shown to be constant, independent of the design speed of the motor. What remains, in order to efficiently use high speed wheels (essential for energy storage) for control purposes, is to reduce rotational losses to acceptable levels. Progress was made in permanent magnet motor design for high speed operation. Variable field motors offer more control flexibility and efficiency over a broader speed range.

Customer loads of two-wheeled vehicles

Science.gov (United States)

Gorges, C.; Öztürk, K.; Liebich, R.

2017-12-01

Customer usage profiles are the most unknown influences in vehicle design targets and they play an important role in durability analysis. This publication presents a customer load acquisition system for two-wheeled vehicles that utilises the vehicle's onboard signals. A road slope estimator was developed to reveal the unknown slope resistance force with the help of a linear Kalman filter. Furthermore, an automated mass estimator was developed to consider the correct vehicle loading. The mass estimation is performed by an extended Kalman filter. Finally, a model-based wheel force calculation was derived, which is based on the superposition of forces calculated from measured onboard signals. The calculated wheel forces were validated by measurements with wheel-load transducers through the comparison of rainflow matrices. The calculated wheel forces correspond with the measured wheel forces in terms of both quality and quantity. The proposed methods can be used to gather field data for improved vehicle design loads.

Assessment of a Boat Fractured Steering Wheel

Directory of Open Access Journals (Sweden)

Vukelic Goran

2016-09-01

Full Text Available During regular use of the steering wheel mounted on a boat, two cracks emanating from a fastener hole were noticed which, consequently, caused final fracture of the wheel. To determine the behavior of a boat steering wheel with cracks present, assessment of a fractured wheel was performed. Torque moments of the fasteners were measured prior to removing the steering wheel from the boat. Visual and dye penetrant inspection followed along with the material detection. Besides using experimental procedures, assessment of the fractured wheel was performed using finite element analysis, i.e. stress intensity factor values were numerically determined. Variation of stress intensity factor with crack length is presented. Possible causes of crack occurrence are given and they include excessive values of fastener torque moments coupled with fretting between fastener and fastener hole that was poorly machined. Results obtained by this assessment can be taken for predicting fracture behavior of a cracked steering wheel and as a reference in the design, mounting and exploitation process of steering wheels improving that way their safety in transportation environment.

The effects of running exercise on oxidative capacity and PGC-1α mRNA levels in the soleus muscle of rats with metabolic syndrome.

Science.gov (United States)

Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Kouzaki, Motoki; Gu, Ning; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

2012-03-01

Skeletal muscles in animals with metabolic syndrome exhibit reduced oxidative capacity. We investigated the effects of running exercise on fiber characteristics, oxidative capacity, and mRNA levels in the soleus muscles of rats with metabolic syndrome [SHR/NDmcr-cp (cp/cp); CP]. We divided 5-week-old CP rats into non-exercise (CP) and exercise (CP-Ex) groups. Wistar-Kyoto rats (WKY) were used as the control group. CP-Ex rats were permitted voluntary exercise on running wheels for 10 weeks. Triglyceride levels were higher and adiponectin levels lower in the CP and CP-Ex groups than in the WKY group. However, triglyceride levels were lower and adiponectin levels higher in the CP-Ex group than in the CP group. The soleus muscles in CP-Ex rats contained only high-oxidative type I fibers, whereas those in WKY and CP rats contained type I, IIA, and IIC fibers. Muscle succinate dehydrogenase (SDH) activity was higher in the CP-Ex group than in the CP group; there was no difference in SDH activity between the WKY and CP-Ex groups. Muscle proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA levels were higher in the CP-Ex group than in the CP group; there was no difference in PGC-1α mRNA levels between the WKY and CP-Ex groups. In CP-Ex rats, longer running distance was associated with increased muscle SDH activity and PGC-1α mRNA levels. We concluded that running exercise restored decreased muscle oxidative capacity and PGC-1α mRNA levels and improved hypertriglyceridemia in rats with metabolic syndrome.

The Effects of Exercise on Expression of CYP19 and StAR mRNA in Steroid-Induced Polycystic Ovaries of Female Rats.

Science.gov (United States)

Aghaie, Fatemeh; Khazali, Homayoun; Hedayati, Mehdi; Akbarnejad, Ali

2018-01-01

Polycystic ovarian syndrome (PCOS) is the most frequent female endocrine disorder that affects 5-10% of women. PCOS is characterized by hyperandrogenism, oligo-/anovulation, and polycystic ovaries. The aim of the present research is to evaluate the expression of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) mRNA in the ovaries of an estradiol valerate (EV)-induced PCOS rat model, and the effect of treadmill and running wheel (voluntary) exercise on these parameters. In this experimental study, we divided adult female Wistar rats that weighed approximately 220 ± 20 g initially into control (n=10) and PCOS (n=30). Subsequently, PCOS group were divided to PCOS, PCOS with treadmill exercise (P-ExT), and PCOS with running wheel exercise (P-ExR) groups (n=10 per group). The expressions of StAR and CYP19 mRNA in the ovaries were determined by quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). Data were analyzed by one-way ANOVA using SPSS software, version 16. The data were assessed at α=0.05. There was significantly lower mRNA expression of CYP19 in the EV-induced PCOS, running wheel and treadmill exercise rats compared to the control group (PStAR in the ovaries of the PCOS group indicated an increasing trend compared to the control group, however this was not statistically significant (P=0.810). We observed that 8 weeks of running wheel and treadmill exercises could not statistically decrease StAR mRNA expression compared to the PCOS group (P=0.632). EV-induced PCOS in rats decreased CYP19 mRNA expression, but had no effect on StAR mRNA expression. We demonstrated that running wheel and moderate treadmill exercise could not modify CYP19 and StAR mRNA expressions. Copyright© by Royan Institute. All rights reserved.

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

International Nuclear Information System (INIS)

Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye

2014-01-01

Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

Forced running exercise attenuates hippocampal neurogenesis impairment and the neurocognitive deficits induced by whole-brain irradiation via the BDNF-mediated pathway

Energy Technology Data Exchange (ETDEWEB)

Ji, Jian-feng; Ji, Sheng-jun; Sun, Rui; Li, Kun; Zhang, Yuan; Zhang, Li-yuan; Tian, Ye, E-mail: dryetian@hotmail.com

2014-01-10

Highlights: •Forced exercise can ameliorate WBI induced cognitive impairment in our rat model. •Mature BDNF plays an important role in the effects of forced exercise. •Exercise may be a possible treatment of the radiation-induced cognitive impairment. -- Abstract: Cranial radiotherapy induces progressive and debilitating cognitive deficits, particularly in long-term cancer survivors, which may in part be caused by the reduction of hippocampal neurogenesis. Previous studies suggested that voluntary exercise can reduce the cognitive impairment caused by radiation therapy. However, there is no study on the effect of forced wheel exercise and little is known about the molecular mechanisms mediating the effect of exercise. In the present study, we investigated whether the forced running exercise after irradiation had the protective effects of the radiation-induced cognitive impairment. Sixty-four Male Sprague–Dawley rats received a single dose of 20 Gy or sham whole-brain irradiation (WBI), behavioral test was evaluated using open field test and Morris water maze at 2 months after irradiation. Half of the rats accepted a 3-week forced running exercise before the behavior detection. Immunofluorescence was used to evaluate the changes in hippocampal neurogenesis and Western blotting was used to assess changes in the levels of mature brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine receptor kinase B (TrkB) receptor, protein kinase B (Akt), extracellular signal-regulated kinase (ERK), calcium-calmodulin dependent kinase (CaMKII), cAMP-calcium response element binding protein (CREB) in the BDNF–pCREB signaling. We found forced running exercise significantly prevented radiation-induced cognitive deficits, ameliorated the impairment of hippocampal neurogenesis and attenuated the down-regulation of these proteins. Moreover, exercise also increased behavioral performance, hippocampal neurogenesis and elevated BDNF–pCREB signaling in non

An Ultrasonic Wheel-Array Probe

Science.gov (United States)

Drinkwater, B. W.; Brotherhood, C. J.; Freemantle, R. J.

2004-02-01

This paper describes the development and modeling of an ultrasonic array wheel probe scanning system. The system operates at 10 MHz using a 64 element array transducer which is 50 mm in length and located in a fluid filled wheel. The wheel is coupled to the test structure dry, or with a small amount of liquid couplant. When the wheel is rolled over the surface of the test structure a defect map (C-Scan) is generated in real-time. The tyre is made from a soft, durable polymer which has very little acoustic loss. Two application studies are presented; the inspection of sealant layers in an aluminum aircraft wing structure and the detection of embedded defects in a thick section carbon composite sample.

Wheeled hopping robot

Science.gov (United States)

Fischer, Gary J [Albuquerque, NM

2010-08-17

The present invention provides robotic vehicles having wheeled and hopping mobilities that are capable of traversing (e.g. by hopping over) obstacles that are large in size relative to the robot and, are capable of operation in unpredictable terrain over long range. The present invention further provides combustion powered linear actuators, which can include latching mechanisms to facilitate pressurized fueling of the actuators, as can be used to provide wheeled vehicles with a hopping mobility.

49 CFR 229.73 - Wheel sets.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Wheel sets. 229.73 Section 229.73 Transportation... TRANSPORTATION RAILROAD LOCOMOTIVE SAFETY STANDARDS Safety Requirements Suspension System § 229.73 Wheel sets. (a...) when applied or turned. (b) The maximum variation in the diameter between any two wheel sets in a three...

Full drive-by-wire dynamic control for four-wheel-steer all-wheel-drive vehicles

Science.gov (United States)

Fahimi, Farbod

2013-03-01

Most of the controllers introduced for four-wheel-steer (4WS) vehicles are derived with the assumption that the longitudinal speed of the vehicle is constant. However, in real applications, the longitudinal speed varies, and the longitudinal, lateral, and yaw dynamics are coupled. In this paper, the longitudinal dynamics of the vehicle as well as its lateral and yaw motions are controlled simultaneously. This way, the effect of driving/braking forces of the tires on the lateral and yaw motions of the vehicle are automatically included in the control laws. To address the dynamic parameter uncertainty of the vehicle, a chatter-free variable structure controller is introduced. Elimination of chatter is achieved by introducing a dynamically adaptive boundary layer thickness. It is shown via simulations that the proposed control approach performs more robustly than the controllers developed based on dynamic models, in which longitudinal speed is assumed to be constant, and only lateral speed and yaw rate are used as system states. Furthermore, this approach supports all-wheel-drive vehicles. Front-wheel-drive or rear-wheel-drive vehicles are also supported as special cases of an all-wheel-drive vehicle.

Three omni-directional wheels control on a mobile robot

OpenAIRE

Ribeiro, António Fernando; Moutinho, Ivo; Silva, Pedro; Fraga, Carlos; Pereira, Nino

2004-01-01

Traditional two wheels differential drive normally used on mobile robots have manoeuvrability limitations and take time to sort out. Most teams use two driving wheels (with one or two cast wheels), four driving wheels and even three driving wheels. A three wheel drive with omni-directional wheel has been tried with success, and was implemented on fast moving autonomous mobile robots. This paper deals with the mathematical kinematics description of such mobile platform, it describes the advant...

Minisatellite Attitude Guidance Using Reaction Wheels

Directory of Open Access Journals (Sweden)

Ion STROE

2015-06-01

Full Text Available In a previous paper [2], the active torques needed for the minisatellite attitude guidance from one fixed attitude posture to another fixed attitude posture were determined using an inverse dynamics method. But when considering reaction/momentum wheels, instead of this active torques computation, the purpose is to compute the angular velocities of the three reaction wheels which ensure the minisatellite to rotate from the initial to the final attitude. This paper presents this computation of reaction wheels angular velocities using a similar inverse dynamics method based on inverting Euler’s equations of motion for a rigid body with one fixed point, written in the framework of the x-y-z sequence of rotations parameterization. For the particular case A=B not equal C of an axisymmetric minisatellite, the two computations are compared: the active torques computation versus the computation of reaction wheels angular velocities ̇x , ̇y and ̇z. An interesting observation comes out from this numerical study: if the three reaction wheels are identical (with Iw the moment of inertia of one reaction wheel with respect to its central axis, then the evolutions in time of the products between Iw and the derivatives of the reaction wheels angular velocities, i.e. ̇ , ̇ and ̇ remain the same and do not depend on the moment of inertia Iw.

Maximum Torque and Momentum Envelopes for Reaction Wheel Arrays

Science.gov (United States)

Markley, F. Landis; Reynolds, Reid G.; Liu, Frank X.; Lebsock, Kenneth L.

2009-01-01

Spacecraft reaction wheel maneuvers are limited by the maximum torque and/or angular momentum that the wheels can provide. For an n-wheel configuration, the torque or momentum envelope can be obtained by projecting the n-dimensional hypercube, representing the domain boundary of individual wheel torques or momenta, into three dimensional space via the 3xn matrix of wheel axes. In this paper, the properties of the projected hypercube are discussed, and algorithms are proposed for determining this maximal torque or momentum envelope for general wheel configurations. Practical strategies for distributing a prescribed torque or momentum among the n wheels are presented, with special emphasis on configurations of four, five, and six wheels.

Moving from voluntary euthanasia to non-voluntary euthanasia: equality and compassion.

Science.gov (United States)

Amaraskekara, Kumar; Bagaric, Mirko

2004-09-01

The recent Dutch law legalising active voluntary euthanasia will reignite the euthanasia debate. An illuminating method for evaluating the moral status of a practice is to follow the implications of the practice to its logical conclusion. The argument for compassion is one of the central arguments in favour of voluntary active euthanasia. This argument applies perhaps even more forcefully in relation to incompetent patients. If active voluntary euthanasia is legalised, arguments based on compassion and equality will be directed towards legalising active non-voluntary euthanasia in order to make accelerated termination of death available also to the incompetent. The removal of discrimination against the incompetent has the potential to become as potent a catch-cry as the right to die. However, the legalisation of non-voluntary euthanasia is undesirable. A review of the relevant authorities reveals that there is no coherent and workable "best interests" test which can be invoked to decide whether an incompetent patient is better off dead. This provides a strong reason for not stepping onto the slippery path of permitting active voluntary euthanasia.

Well-to-wheel analysis of direct and indirect use of natural gas in passenger vehicles

International Nuclear Information System (INIS)

Curran, Scott J.; Wagner, Robert M.; Graves, Ronald L.; Keller, Martin; Green, Johney B.

2014-01-01

The abundance of natural gas in the United States because of the number of existing natural gas reserves and the recent advances in extracting unconventional reserves has been one of the main drivers for low natural gas prices. A question arises of what is the optimal use of natural gas as a transportation fuel. Is it more efficient to use natural gas in a stationary power application to generate electricity to charge electric vehicles, compress natural gas for onboard combustion in vehicles, or re-form natural gas into a denser transportation fuel? This study investigates the well-to-wheels energy use and greenhouse gas emissions from various natural gas to transportation fuel pathways and compares the results to conventional gasoline vehicles and electric vehicles using the US electrical generation mix. Specifically, natural gas vehicles running on compressed natural gas are compared against electric vehicles charged with electricity produced solely from natural gas combustion in stationary power plants. The results of the study show that the dependency on the combustion efficiency of natural gas in stationary power can outweigh the inherent efficiency of electric vehicles, thus highlighting the importance of examining energy use on a well-to-wheels basis. - Highlights: • Well-to-wheels analysis shows differences in use of natural gas for transportation. • Well-to-wheels approach needed to evaluate total energy use and greenhouse gas emissions. • Well-to-wheels energy and GHG (greenhouse gas) emissions depend on efficiency of the prime mover. • Efficiency of power generation critical for low GHG emissions with electric vehicles. • Fuel economy critical for low GHG emissions with compressed natural gas vehicles

The PS locomotive runs again

CERN Multimedia

2001-01-01

Over forty years ago, the PS train entered service to steer the magnets of the accelerator into place... ... a service that was resumed last Tuesday. Left to right: Raymond Brown (CERN), Claude Tholomier (D.B.S.), Marcel Genolin (CERN), Gérard Saumade (D.B.S.), Ingo Ruehl (CERN), Olivier Carlier (D.B.S.), Patrick Poisot (D.B.S.), Christian Recour (D.B.S.). It is more than ten years since people at CERN heard the rumbling of the old PS train's steel wheels. Last Tuesday, the locomotive came back into service to be tested. It is nothing like the monstrous steel engines still running on conventional railways -just a small electric battery-driven vehicle employed on installing the magnets for the PS accelerator more than 40 years ago. To do so, it used the tracks that run round the accelerator. In fact, it is the grandfather of the LEP monorail. After PS was commissioned in 1959, the little train was used more and more rarely. This is because magnets never break down, or hardly ever! In fact, the loc...

Interplay between exercise and dietary fat modulates myelinogenesis in the central nervous system

OpenAIRE

Yoon, Hyesook; Kleven, Andrew; Paulsen, Alex; Kleppe, Laurel; Wu, Jianmin; Ying, Zhe; Gomez-Pinilla, Fernando; Scarisbrick, Isobel A.

2016-01-01

Here we show that the interplay between exercise training and dietary fat regulates myelinogenesis in the adult central nervous system. Mice consuming high fat with coordinate voluntary running wheel exercise for 7 weeks showed increases in the abundance of the major myelin membrane proteins, proteolipid (PLP) and myelin basic protein (MBP), in the lumbosacral spinal cord. Expression of MBP and PLP RNA, as well that for Myrf1, a transcription factor driving oligodendrocyte differentiation wer...

Exercise training in transgenic mice is associated with attenuation of early breast cancer growth in a dose-dependent manner.

Directory of Open Access Journals (Sweden)

Jorming Goh

Full Text Available Epidemiological research suggests that regular physical activity confers beneficial effects that mediate an anti-tumor response and may reduce cancer recurrence. It is unclear what amount of physical activity is necessary to exert such a protective effect and what mechanisms are involved. We investigated the effects of voluntary wheel running on tumor progression and cytokine gene expression in the transgenic polyoma middle T oncoprotein (PyMT mouse model of invasive breast cancer. Runners showed significantly reduced tumor sizes compared with non-runners after 3 weeks of running (p ≤ 0.01, and the greater the running distance the smaller the tumor size (Pearson's r = -0.61, p ≤ 0.04, R(2 = 0.38. Mice running greater than 150 km per week had a significantly attenuated tumor size compared with non-runners (p ≤ 0.05. Adipose tissue mass was inversely correlated with tumor size in runners (Pearson's r = -0.77, p = 0.014 but not non-runners. Gene expression of CCL22, a cytokine associated with recruitment of immunosuppressive T regulatory cells, was decreased in tumors of runners compared to non-runners (p ≤ 0.005. No differences in tumor burden or metastatic burden were observed between runners and non-runners after ten weeks of running when the study was completed. We conclude that voluntary wheel running in PyMT mice correlates with an attenuation in tumor progression early during the course of invasive breast cancer. This effect is absent in the later stages of overwhelming tumor burden even though cytokine signaling for immunosuppressive regulatory T cells was down regulated. These observations suggest that the initiation of moderate exercise training for adjunctive therapeutic benefit early in the course of invasive breast cancer should be considered for further investigation.

Module-based structure design of wheeled mobile robot

Directory of Open Access Journals (Sweden)

Z. Luo

2018-02-01

Full Text Available This paper proposes an innovative and systematic approach for synthesizing mechanical structures of wheeled mobile robots. The principle and terminologies used for the proposed synthesis method are presented by adopting the concept of modular design, isomorphic and non-isomorphic, and set theory with its associated combinatorial mathematics. The modular-based innovative synthesis and design of wheeled robots were conducted at two levels. Firstly at the module level, by creative design and analysing the structures of classic wheeled robots, a wheel module set containing four types of wheel mechanisms, a suspension module set consisting of five types of suspension frames and a chassis module set composed of five types of rigid or articulated chassis were designed and generalized. Secondly at the synthesis level, two kinds of structure synthesis modes, namely the isomorphic-combination mode and the non-isomorphic combination mode were proposed to synthesize mechanical structures of wheeled robots; which led to 241 structures for wheeled mobile robots including 236 novel ones. Further, mathematical models and a software platform were developed to provide appropriate and intuitive tools for simulating and evaluating performance of the wheeled robots that were proposed in this paper. Eventually, physical prototypes of sample wheeled robots/rovers were developed and tested so as to prove and validate the principle and methodology presented in this paper.

Mathematical Modeling of the Braking System of Wheeled Mainline Aircraft

Directory of Open Access Journals (Sweden)

I. S. Shumilov

2016-01-01

Full Text Available The braking system of the landing gear wheels of a mainline aircraft has to meet mandatory requirements laid out in the Aviation Regulations AP-25 (Para 25.735. «Brakes and brake systems". These requirements are essential when creating the landing gear wheel brake control system (WBCS and are used as main initial data in its mathematical modeling. The WBCS is one of the most important systems to ensure the safe completion of the flight. It is a complex of devices, i.e. units (hydraulic, electrical, and mechanical, connected through piping, wiring, mechanical constraints. This complex should allow optimizing the braking process when a large number of parameters change. The most important of them are the following: runway friction coefficient (RFC, lifting force, weight and of the aircraft, etc. The main structural elements involved in braking the aircraft are: aircraft wheels with pneumatics (air tires and brake discs, WBCS, and cooling system of gear wheels when braking.To consider the aircraft deceleration on the landing run is of essence at the stage of design, development, and improvement of brakes and braking systems. Based on analysis of equation of the aircraft motion and energy balance can be determined energy loading and its basic design parameters, braking distances and braking time.As practice and analysis of energy loading show, they (brake + wheel absorb the aircraftpossessed kinetic energy at the start of braking as much as 60-70%, 70-80%, and 80-90%, respectively, under normal increased, and emergency operating conditions. The paper presents a procedure for the rapid calculation of energy loading of the brake wheel.Currently, the mainline aircrafts use mainly electrohydraulic brake systems in which there are the main, backup, and emergency-parking brake systems. All channels are equipped with automatic anti-skid systems. Their presence in the emergency (the third reserve channel significantly improves the reliability and safety of

Exercise restores decreased physical activity levels and increases markers of autophagy and oxidative capacity in myostatin/activin-blocked mdx mice.

Science.gov (United States)

Hulmi, Juha J; Oliveira, Bernardo M; Silvennoinen, Mika; Hoogaars, Willem M H; Pasternack, Arja; Kainulainen, Heikki; Ritvos, Olli

2013-07-15

The importance of adequate levels of muscle size and function and physical activity is widely recognized. Myostatin/activin blocking increases skeletal muscle mass but may decrease muscle oxidative capacity and can thus be hypothesized to affect voluntary physical activity. Soluble activin receptor IIB (sActRIIB-Fc) was produced to block myostatin/activins. Modestly dystrophic mdx mice were injected with sActRIIB-Fc or PBS with or without voluntary wheel running exercise for 7 wk. Healthy mice served as controls. Running for 7 wk attenuated the sActRIIB-Fc-induced increase in body mass by decreasing fat mass. Running also enhanced/restored the markers of muscle oxidative capacity and autophagy in mdx mice to or above the levels of healthy mice. Voluntary running activity was decreased by sActRIIB-Fc during the first 3-4 wk correlating with increased body mass. Home cage physical activity of mice, quantified from the force plate signal, was decreased by sActRIIB-Fc the whole 7-wk treatment in sedentary mice. To understand what happens during the first weeks after sActRIIB-Fc administration, when mice are less active, healthy mice were injected with sActRIIB-Fc or PBS for 2 wk. During the sActRIIB-Fc-induced rapid 2-wk muscle growth period, oxidative capacity and autophagy were reduced, which may possibly explain the decreased running activity. These results show that increased muscle size and decreased markers of oxidative capacity and autophagy during the first weeks of myostatin/activin blocking are associated with decreased voluntary activity levels. Voluntary exercise in dystrophic mice enhances the markers of oxidative capacity and autophagy to or above the levels of healthy mice.

Developments of 207Pb, 208Pb and 209Bi target wheels in the synthesis of 107Ns, 108Hs and 109Mt

International Nuclear Information System (INIS)

Folger, H.; Hartmann, W.; Hessberger, F.P.; Hofmann, S.; Klemm, J.; Muenzenberg, G.; Ninov, V.; Schmidt, K.H.; Schoett, H.J.; Thalheimer, W.; Armbruster, P.

1993-05-01

The developments of 207 Pb, 208 Pb and 209 Bi target wheels and their applications in heavy-ion fusion reactions are reviewed. In both, fabrication and use, the centers of the evaporator or accelerator beams are focussed at wheel radii of 155 mm to specially shaped frames which generate very homogeneous target layers and very constant reaction and counting rates in the experiment. Target areas of up to ∼98% of a wheel's circumference of 974 mm can be provided. The preparation procedures for necessary C backings and protecting layers of C are described, and details are given for the developments of high-vacuum evaporations of 207 Pb, 208 Pb and 209 Bi with deposition yields of 35-55% from tantalum crucibles. The applications of the target wheels in heavy-ion fusion reactions with beams of 54 Cr and 58 Fe at energies near the Coulomb barrier and intensities of ∼10 12 particles/s are mentioned. The target parameters for the production runs of the new chemical elements 107 Ns, 108 Hs and 109 Mt are included. (orig.)

Costs associated with wheeling

International Nuclear Information System (INIS)

Anon.

1991-01-01

Wheeling costs are incurred by all companies that experience a change in power flows over their transmission lines during a specific transaction, whether or not the lines of that company are part of the contract path. The costs of providing wheeling service differ from one system to another and from one kind of wheeling transaction to another. While most transactions may be completed using existing capacity, others may require an increase in line. Depending on the situation, some cost components may be high, low, negative, or not incurred at all. This article discusses two general categories of costs; transactional and capital. The former are all operation, maintenance and opportunity costs incurred in completing a specific transaction assuming the existence of adequate capacity. Capital costs are the costs of major new equipment purchases and lines necessary to provide any increased level of transmission services

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change.

Science.gov (United States)

Rinnankoski-Tuikka, Rita; Hulmi, Juha J; Torvinen, Sira; Silvennoinen, Mika; Lehti, Maarit; Kivelä, Riikka; Reunanen, Hilkka; Kujala, Urho M; Kainulainen, Heikki

2014-08-01

The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skeletal muscle were also investigated. During a 19-week experiment, C57BL/6J mice were studied in six different groups: low-fat diet sedentary, low-fat diet active, high-fat diet sedentary, high-fat diet active and two groups which were high-fat sedentary for nine weeks, after which divided into low-fat sedentary or low-fat active groups. Myocellular triglyceride concentration and perilipin protein expression levels were assessed. We show that, concurrently with impaired insulin sensitivity, the expression level of PLIN5 and muscular triglyceride concentration increased dramatically after high-fat diet. These adaptations were reversible after the diet change intervention with no additional effect of exercise. After high-fat diet, lipid droplets become larger providing more surface area for PLIN5. We suggest that PLIN5 is an important regulator of lipid droplet turnover in altered conditions of fatty acid supply and consumption. Imbalances in lipid droplet metabolism and turnover might lead to lipotoxicity-related insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Activation pattern of ACE2/Ang-(1-7) and ACE/Ang II pathway in course of heart failure assessed by multiparametric MRI in vivo in Tgαq*44 mice.

Science.gov (United States)

Tyrankiewicz, Urszula; Olkowicz, Mariola; Skórka, Tomasz; Jablonska, Magdalena; Orzylowska, Anna; Bar, Anna; Gonet, Michal; Berkowicz, Piotr; Jasinski, Krzysztof; Zoladz, Jerzy A; Smolenski, Ryszard T; Chlopicki, Stefan

2018-01-01

Here, we analyzed systemic (plasma) and local (heart/aorta) changes in ACE/ACE-2 balance in Tgαq*44 mice in course of heart failure (HF). Tgαq*44 mice with cardiomyocyte-specific Gαq overexpression and late onset of HF were analyzed at different age for angiotensin pattern in plasma, heart, and aorta using liquid chromatography/mass spectrometry, for progression of HF by in vivo magnetic resonance imaging under isoflurane anesthesia, and for physical activity by voluntary wheel running. Six-month-old Tgαq*44 mice displayed decreased ventricle radial strains and impaired left atrial function. At 8-10 mo, Tgαq*44 mice showed impaired systolic performance and reduced voluntary wheel running but exhibited preserved inotropic reserve. At 12 mo, Tgαq*44 mice demonstrated a severe impairment of basal cardiac performance and modestly compromised inotropic reserve with reduced voluntary wheel running. Angiotensin analysis in plasma revealed an increase in concentration of angiotensin-(1-7) in 6- to 10-mo-old Tgαq*44 mice. However, in 12- to 14-mo-old Tgαq*44 mice, increased angiotensin II was noted with a concomitant increase in Ang III, Ang IV, angiotensin A, and angiotensin-(1-10). The pattern of changes in the heart and aorta was also compatible with activation of ACE2, followed by activation of the ACE pathway. In conclusion, mice with cardiomyocyte Gαq protein overexpression develop HF that is associated with activation of the systemic and the local ACE/Ang II pathway. However, it is counterbalanced by a prominent ACE2/Ang-(1-7) activation, possibly allowing to delay decompensation. NEW & NOTEWORTHY Changes in ACE/ACE-2 balance were analyzed based on measurements of a panel of nine angiotensins in plasma, heart, and aorta of Tgαq*44 mice in relation to progression of heart failure (HF) characterized by multiparametric MRI and exercise performance. The early stage of HF was associated with upregulation of the ACE2/angiotensin-(1-7) pathway, whereas the end

Support for Voluntary Euthanasia with No Logical Slippery Slope to Non-Voluntary Euthanasia.

Science.gov (United States)

Daskal, Steven

2018-01-01

This paper demonstrates that acceptance of voluntary euthanasia does not generate commitment to either non-voluntary euthanasia or euthanasia on request. This is accomplished through analysis of John Keown's and David Jones's slippery slope arguments, and rejection of their view that voluntary euthanasia requires physicians to judge patients as better off dead. Instead, voluntary euthanasia merely requires physicians to judge patients as within boundaries of appropriate deference. This paper develops two ways of understanding and defending voluntary euthanasia on this model, one focused on the independent value of patients' autonomy and the other on the evidence of well-being provided by patients' requests. Both avoid the purported slippery slopes and both are independently supported by an analogy to uncontroversial elements of medical practice. Moreover, the proposed analyses of voluntary euthanasia suggest parameters for the design of euthanasia legislation, both supporting and challenging elements of existing laws in Oregon and the Netherlands.

Study on design of light-weight super-abrasive wheel

Science.gov (United States)

Nohara, K.; Yanagihara, K.; Ogawa, M.

2018-01-01

Fixed-abrasive tool, also called a grinding wheel, is produced by furnacing abrasive compound which contains abrasive grains and binding powder such as vitrified materials or resins. Fixed-abrasive tool is installed on spindle of grinding machine. And it is given 1,800-2,000 min-1 of spindle rotation for the usage. The centrifugal fracture of the compound of fixed- abrasive tool is one of the careful respects in designing. In recent years, however, super-abrasive wheel as a fixed-abrasive tool has been developed and applied widely. One of the most characteristic respects is that metal is applied for the body of grinding-wheel. The strength to hold abrasive grain and the rigidity of wheel become stronger than those of general grinding wheel, also the lifespan of fixed-abrasive tool becomes longer. The weight of fixed-abrasive tool, however, becomes heavier. Therefore, when the super-abrasive wheel is used, the power consumption of spindle motor becomes larger. It also becomes difficult for the grinding-wheel to respond to sudden acceleration or deceleration. Thus, in order to reduce power consumption in grinding and to obtain quicker frequency response of super-abrasive wheel, the new wheel design is proposed. The design accomplishes 46% weight reduction. Acceleration that is one second quicker than that of conventional grinding wheel is obtained.

Aerodynamic analysis of an isolated vehicle wheel

Science.gov (United States)

Leśniewicz, P.; Kulak, M.; Karczewski, M.

2014-08-01

Increasing fuel prices force the manufacturers to look into all aspects of car aerodynamics including wheels, tyres and rims in order to minimize their drag. By diminishing the aerodynamic drag of vehicle the fuel consumption will decrease, while driving safety and comfort will improve. In order to properly illustrate the impact of a rotating wheel aerodynamics on the car body, precise analysis of an isolated wheel should be performed beforehand. In order to represent wheel rotation in contact with the ground, presented CFD simulations included Moving Wall boundary as well as Multiple Reference Frame should be performed. Sliding mesh approach is favoured but too costly at the moment. Global and local flow quantities obtained during simulations were compared to an experiment in order to assess the validity of the numerical model. Results of investigation illustrates dependency between type of simulation and coefficients (drag and lift). MRF approach proved to be a better solution giving result closer to experiment. Investigation of the model with contact area between the wheel and the ground helps to illustrate the impact of rotating wheel aerodynamics on the car body.

Aerodynamic analysis of an isolated vehicle wheel

International Nuclear Information System (INIS)

Leśniewicz, P; Kulak, M; Karczewski, M

2014-01-01

Increasing fuel prices force the manufacturers to look into all aspects of car aerodynamics including wheels, tyres and rims in order to minimize their drag. By diminishing the aerodynamic drag of vehicle the fuel consumption will decrease, while driving safety and comfort will improve. In order to properly illustrate the impact of a rotating wheel aerodynamics on the car body, precise analysis of an isolated wheel should be performed beforehand. In order to represent wheel rotation in contact with the ground, presented CFD simulations included Moving Wall boundary as well as Multiple Reference Frame should be performed. Sliding mesh approach is favoured but too costly at the moment. Global and local flow quantities obtained during simulations were compared to an experiment in order to assess the validity of the numerical model. Results of investigation illustrates dependency between type of simulation and coefficients (drag and lift). MRF approach proved to be a better solution giving result closer to experiment. Investigation of the model with contact area between the wheel and the ground helps to illustrate the impact of rotating wheel aerodynamics on the car body.

Development of public health program for type 1 diabetes in a university community: preliminary evaluation of behavioural change wheel.

Science.gov (United States)

Nwose, Ezekiel Uba; Digban, K A; Anyasodor, A E; Bwititi, P T; Richards, R S; Igumbor, E O

2017-10-23

Diabetes mellitus, including type 1 is a global public health problem among the young persons. While public health campaign and screening program is a potential strategy, but communication skills, knowledge and opinion of the healthcare personnel are indicated as variables that can impact patient's education, which will lead to better outcome of care. Thus, in designing or planning a program for public health, workforce development considers opinion and behavioural change wheel of prospective personnel. The purpose of this preliminary study was to evaluate if a university academic department has the behavioural change wheel to function as workforce infrastructure for an envisioned program. Survey of knowledge, attitude and practice (KAP) of a university community regarding diabetes type 1 was performed. The KAP were translated into behavioural change wheel comprising capacity, motivation and opportunity (CMO). There are baseline indications of the behavioural change wheel potential of the public health department to run a T1D screening program. The number of participants who knew someone with T1D was significantly higher than the subgroup with no such knowledge (pwheel or CMO to develop a workforce infrastructure for T1D screening program, the experience that comes with age of lecturers will be an important factor to enable such program to succeed.

First Wheel of the Hadronic EndCap Calorimeter Completed

CERN Multimedia

Oram, C.J.

2002-01-01

With the LAr calorimeters well advanced in module production, the attention is turning to Batiment 180 where the calorimeter modules are formed into complete detectors and inserted into their respective cryostats. For the Hadronic End Cap (HEC) Group the task in B180 is to assemble the wheels, rotate them into their final orientation, and put them onto the cradle in front of the End Cap Cryostat. These tasks have been completed for the first HEC wheel in the B180 End Cap Clean Room. Given that this wheel weighs 70 tons the group is very relieved to have established that these gymnastics with the wheel proceed in a routine fashion. To assemble a wheel we take modules that have already been cold tested, do the final electrical testing and locate them onto the HEC wheel assembly table. Four wheels are required in total, each consisting of 32 modules. Wheel assembly is done in the horizontal position, creating a doughnut-like object sitting on the HEC table. The first picture shows the last module being added ...

Project considerations and design of systems for wheeling cogenerated power

Energy Technology Data Exchange (ETDEWEB)

Tessmer, R.G. Jr.; Boyle, J.R.; Fish, J.H. III; Martin, W.A.

1994-08-01

Wheeling electric power, the transmission of electricity not owned by an electric utility over its transmission lines, is a term not generally recognized outside the electric utility industry. Investigation of the term`s origin is intriguing. For centuries, wheel has been used to describe an entire machine, not just individual wheels within a machine. Thus we have waterwheel, spinning wheel, potter`s wheel and, for an automobile, wheels. Wheel as a verb connotes transmission or modification of forces and motion in machinery. With the advent of an understanding of electricity, use of the word wheel was extended to be transmission of electric power as well as mechanical power. Today, use of the term wheeling electric power is restricted to utility transmission of power that it doesn`t own. Cogeneration refers to simultaneous production of electric and thermal power from an energy source. This is more efficient than separate production of electricity and thermal power and, in many instances, less expensive.

Phenomena of Foamed Concrete under Rolling of Aircraft Wheels

Science.gov (United States)

Jiang, Chun-shui; Yao, Hong-yu; Xiao, Xian-bo; Kong, Xiang-jun; Shi, Ya-jie

2014-04-01

Engineered Material Arresting System (EMAS) is an effective technique to reduce hazards associated with aircraft overrunning runway. In order to ascertain phenomena of the foamed concrete used for EMAS under rolling of aircraft wheel, a specially designed experimental setup was built which employed Boeing 737 aircraft wheels bearing actual vertical loads to roll through the foamed concrete. A number of experiments were conducted upon this setup. It is discovered that the wheel rolls the concrete in a pure rolling manner and crushes the concrete downwards, instead of crushing it forward, as long as the concrete is not higher than the wheel axle. The concrete is compressed into powder in-situ by the wheel and then is brought to bottom of the wheel. The powder under the wheel is loose and thus is not able to sustain wheel braking. It is also found that after being rolled by the wheel the concrete exhibits either of two states, i.e. either 'crushed through' whole thickness of the concrete or 'crushed halfway', depending on combination of strength of the concrete, thickness of the concrete, vertical load the wheel carries, tire dimension and tire pressure. A new EMAS design concept is developed that if an EMAS design results in the 'crushed through' state for the main gears while the 'crushed halfway' state for the nose gear, the arresting bed would be optimal to accommodate the large difference in strength between the nose gear and the main gear of an aircraft.

The empirical slippery slope from voluntary to non-voluntary euthanasia.

Science.gov (United States)

Lewis, Penney

2007-01-01

This article examines the evidence for the empirical argument that there is a slippery slope between the legalization of voluntary and non-voluntary euthanasia. The main source of evidence in relation to this argument comes from the Netherlands. The argument is only effective against legalization if it is legalization which causes the slippery slope. Moreover, it is only effective if it is used comparatively-to show that the slope is more slippery in jurisdictions which have legalized voluntary euthanasia than it is in jurisdictions which have not done so. Both of these elements are examined comparatively.

A fully omnidirectional wheeled assembly for robotic vehicles

International Nuclear Information System (INIS)

Killough, S.M.; Pin, F.G.

1990-01-01

A large number of wheeled or tracked platform mechanisms have been studied and developed to provide their mobility capability to teleoperated and autonomous robot vehicles. This paper presents an original wheeled platform based on an orthogonal wheel assembly that provides a full (three-degrees-of-freedom) omnidirectionality of the platform without wheel slippage and with the capability for simultaneous motions in rotation and translation (including sideways movements). A schematic of the basic wheel assembly is shown. The motion of the assembly is unconstrained (freewheeling) in the direction parallel to the main assembly shaft, while it is constrained in the direction perpendicular to the shaft, being driven in this direction by rotation of the shaft. A prototype platform was constructed to demonstrate the feasibility of this new concept

Reaction Wheel Disturbance Model Extraction Software - RWDMES

Science.gov (United States)

Blaurock, Carl

2009-01-01

The RWDMES is a tool for modeling the disturbances imparted on spacecraft by spinning reaction wheels. Reaction wheels are usually the largest disturbance source on a precision pointing spacecraft, and can be the dominating source of pointing error. Accurate knowledge of the disturbance environment is critical to accurate prediction of the pointing performance. In the past, it has been difficult to extract an accurate wheel disturbance model since the forcing mechanisms are difficult to model physically, and the forcing amplitudes are filtered by the dynamics of the reaction wheel. RWDMES captures the wheel-induced disturbances using a hybrid physical/empirical model that is extracted directly from measured forcing data. The empirical models capture the tonal forces that occur at harmonics of the spin rate, and the broadband forces that arise from random effects. The empirical forcing functions are filtered by a physical model of the wheel structure that includes spin-rate-dependent moments (gyroscopic terms). The resulting hybrid model creates a highly accurate prediction of wheel-induced forces. It accounts for variation in disturbance frequency, as well as the shifts in structural amplification by the whirl modes, as the spin rate changes. This software provides a point-and-click environment for producing accurate models with minimal user effort. Where conventional approaches may take weeks to produce a model of variable quality, RWDMES can create a demonstrably high accuracy model in two hours. The software consists of a graphical user interface (GUI) that enables the user to specify all analysis parameters, to evaluate analysis results and to iteratively refine the model. Underlying algorithms automatically extract disturbance harmonics, initialize and tune harmonic models, and initialize and tune broadband noise models. The component steps are described in the RWDMES user s guide and include: converting time domain data to waterfall PSDs (power spectral

Control of wheeled mobile robot in restricted environment

Science.gov (United States)

Ali, Mohammed A. H.; En, Chang Yong

2018-03-01

This paper presents a simulation and practical control system for wheeled mobile robot in restricted environment. A wheeled mobile robot with 3 wheels is fabricated and controlled by proportional derivative active force control (PD-AFC) to move in a pre-planned restricted environment to maintain the tracking errors at zero level. A control system with two loops, outer by PD controller and inner loop by Active Force Control, are designed to control the wheeled mobile robot. Fuzzy logic controller is implemented in the Active force Control to estimate the inertia matrix that will be used to calculate the actual torque applied on the wheeled mobile robot. The mobile robot is tested in two different trajectories, namely are circular and straight path. The actual path and desired path are compared.

Nonlinear analysis of the GFRP material wheel hub

Directory of Open Access Journals (Sweden)

Dong Yun-Feng

2015-01-01

Full Text Available In this paper, the current bicycle wheel was replaced by the ones which composed by the wheel hub with Glassfiber Reinforced Plastic (alkali free thin-walled cylinder material, hereinafter referred to as GFRP material and the protective components made up of rubber outer pneumatic pad. With the help of the basic theory of elastic-plastic mechanics, the finite element “Nonlinear buckling” analysis of the wheel was carried out. The results show that the maximum elastic deformation of the wheel hub and the critical value of buckling failure load were restricted by the elasticity under the condition of external loads. Considering with the tensile strength and elastic modulus of the GFRP value of the material, it is demonstrated that the material is feasible to be used for wheel hub.

Meals on Wheels Association of America

Science.gov (United States)

... Meals About Meals on Wheels Get Started The Issue The Problem & Our Solution Meals on Wheels Health Facts & Resources Senior Facts Map State Fact Sheets Research More Than a Meal Pilot Research Study Medicare Claims Analyses Policy Myths Hunger in Older Adults Take Action Volunteer Advocate #SAVELUNCH ...

ANALYSIS OF FORMING TREAD WHEEL SETS

Directory of Open Access Journals (Sweden)

Igor IVANOV

2017-09-01

Full Text Available This paper shows the results of a theoretical study of profile high-speed grinding (PHSG for forming tread wheel sets during repair instead of turning and mold-milling. Significant disadvantages of these methods are low capacity to adapt to the tool and inhomogeneous structure of the wheel material. This leads to understated treatment regimens and difficulties in recovering wheel sets with thermal and mechanical defects. This study carried out modeling and analysis of emerging cutting forces. Proposed algorithms describe the random occurrence of the components of the cutting forces in the restoration profile of wheel sets with an inhomogeneous structure of the material. To identify the statistical features of randomly generated structures fractal dimension and the method of random additions were used. The multifractal spectrum formed is decomposed into monofractals by wavelet transform. The proposed method allows you to create the preconditions for controlling the parameters of the treatment process.

Development of Diamond-like Carbon Fibre Wheel

Institute of Scientific and Technical Information of China (English)

魏源迁; 山口勝美; 洞口巌; 竹内雅之

2004-01-01

A unique diamond-like carbon (DLC) grinding wheel was developed, in which the DLC fibres were made by rolling Al sheets coated with DLC films and aligned normally to the grinding wheel surface by laminating Al sheets together with DLC fibres. In this paper, the formation process of DLC fibres and the fabrication process of a DLC fibre wheel were investigated. Many grinding experiments were also carried out on a precision NC plane milling machine using a newly developed DLC wheel. Grinding of specimens of silicon wafers, optical glasses, quartz, granites and hardened die steel SKD11 demonstrated the capabilities of nanometer surface finish. A smooth surface with a roughness value of Ra2.5nm (Ry26nm) was achieved.

UT Biomedical Informatics Lab (BMIL) probability wheel

Science.gov (United States)

Huang, Sheng-Cheng; Lee, Sara; Wang, Allen; Cantor, Scott B.; Sun, Clement; Fan, Kaili; Reece, Gregory P.; Kim, Min Soon; Markey, Mia K.

A probability wheel app is intended to facilitate communication between two people, an "investigator" and a "participant", about uncertainties inherent in decision-making. Traditionally, a probability wheel is a mechanical prop with two colored slices. A user adjusts the sizes of the slices to indicate the relative value of the probabilities assigned to them. A probability wheel can improve the adjustment process and attenuate the effect of anchoring bias when it is used to estimate or communicate probabilities of outcomes. The goal of this work was to develop a mobile application of the probability wheel that is portable, easily available, and more versatile. We provide a motivating example from medical decision-making, but the tool is widely applicable for researchers in the decision sciences.

Wheeling rates evaluation using optimal power flows

International Nuclear Information System (INIS)

Muchayi, M.; El-Hawary, M. E.

1998-01-01

Wheeling is the transmission of electrical power and reactive power from a seller to a buyer through a transmission network owned by a third party. The wheeling rates are then the prices charged by the third party for the use of its network. This paper proposes and evaluates a strategy for pricing wheeling power using a pricing algorithm that in addition to the fuel cost for generation incorporates the optimal allocation of the transmission system operating cost, based on time-of-use pricing. The algorithm is implemented for the IEEE standard 14 and 30 bus system which involves solving a modified optimal power flow problem iteratively. The base of the proposed algorithm is the hourly spot price. The analysis spans a total time period of 24 hours. Unlike other algorithms that use DC models, the proposed model captures wheeling rates of both real and reactive power. Based on the evaluation, it was concluded that the model has the potential for wide application in calculating wheeling rates in a deregulated competitive power transmission environment. 9 refs., 3 tabs

To the question of modeling of wheels and rails wear processes

Directory of Open Access Journals (Sweden)

S.V. Myamlin

2013-06-01

Full Text Available Purpose. There is a need of wear process modeling in the wheel-rail system. This is related to the fact that the wear processes in this system are absolutely different in the initial and final stages. The profile change of rail and, especially, of the wheels caused by the wear significantly affects the rolling stock dynamics, traffic safety and the resource of the wheels and rails. Wear modeling and the traffic safety evaluation requires the accounting of the low frequency component forces (including the modeling of transitional areas affecting the wheel on the side of the rail and carriage in motion of rolling stock, so the statistical analysis is not possible. Methodology. The method of mathematical modeling of the wheel set and the rail interaction was used during the research conducting. Findings. As a result of the modeling of the wheel set motion on the rail track, the mathematic model with 19 freedom degrees was obtained. This model takes into account the axle torque and studies wheels constructions as the components of the mechanical systems, consisting of a hub and tire. Originality. The mathematic model allows evaluating the wear degree of the wheels and rails when using on the rolling stock not only all-metal wheel sets, but also compound ones with the use of spring wheels and independent rotation of semi-axes with the wheels. Practical value. The development of the improved mathematical model of freight car wheel set motion with differential rotation of the wheels and compound axles allows studying the wear processes of wheels and rails.

Finite element analysis of rail-wheel interaction

International Nuclear Information System (INIS)

Rahman, F.; Kharlamov, Y.A.; Islam, S.; Khan, A.A.

2006-01-01

Damage mechanisms such as surface cracks, plastic deformation and wear can significantly reduce the service life of railway track and rolling stock. They also have a negative impact on the rolling noise as well as: on the riding comfort. A proper understanding of these mechanisms requires a detailed knowledge of physical interaction between wheel and rail. Furthermore, demands for higher train speeds and increased axle loads implies that the consequences of larger contact. forces between wheel and rail must be thoroughly investigated. Two methods have traditionally been used to investigate the rail-wheel contact, that is the Hertz analytical method and simplified numerical method based on the boundary element (BE) method. These methods rely on a half-space assumption and a linear material model. This paper presents that to overcome these limitations, a tool for FE-based quasistatic wheel-rail contact simulations has been developed. The tool is a library of ANSYS macro routines for configuring, meshing and loading of a parametric wheel-rail model. The meshing is based on measured wheel and rail profiles. The wheel and rail materials in the contact region are treated as elastic-plastic with kinematic hardening. By controlling the values of the configuration parameters, representations of various driving cases can be generated. The quasi-static loads are obtained from train motion. Interaction phenomena such as rolling, spinning and sidling can be included. The modeling tool and a methodology are described in the presented paper. Significant differences in the calculated state between the FE solution and the traditional approaches can be observed. These differences are most significant in situations with flange contact. (author)