Voluntary Exercise Group Research Articles

Exercise maintains euglycemia in association with decreased activation of c-Jun NH2-terminal kinase and serine phosphorylation of IRS-1 in the liver of ZDF rats

Stress-activated systems and oxidative stress are involved in insulin resistance, which, along with beta-cell failure, contribute to the development of type 2 diabetes mellitus (T2DM). Exercise improves insulin resistance and glucose tolerance, and these adaptations may, in part, be related to reductions in inflammation and oxidative stress. We investigated circulating and tissue-specific markers of inflammation and oxidative stress and insulin-signaling pathways in a rodent model of T2DM, the Zucker diabetic fatty rat, with and without voluntary exercise. At 5 wk of age, Zucker diabetic fatty rats (n = 8-9/group) were divided into basal (B), voluntary exercise (E), and sedentary control (S) groups. B rats were euthanized at 6 wk of age, and S and E rats were euthanized 10 wk later. E rats ran approximately 5 km/day, which improved insulin sensitivity and maintained fed and fasted glucose levels and glucose tolerance. Ten weeks of exercise also decreased whole body markers of inflammation and oxidative stress in plasma and liver, including lowered circulating IL-6, haptoglobin, and malondialdehyde levels, hepatic protein oxidation, and phosphorylated JNK, the latter indicating decreased JNK activity. Hepatic phosphoenolpyruvate carboxykinase levels and Ser(307)-phosphorylated insulin receptor substrate-1 were also reduced in E compared with S rats. In summary, we show that, in a rodent model of T2DM, voluntary exercise decreases circulating markers of inflammation and oxidative stress and lowers hepatic JNK activation and Ser(307)-phosphorylated insulin receptor substrate-1. These changes in oxidative stress markers and inflammation are associated with decreased hyperglycemia and insulin resistance and reduced expression of the main gluconeogenic enzyme phosphoenolpyruvate carboxykinase.

Phytase supplementation increases bone mineral density, lean body mass and voluntary physical activity in rats fed a low-zinc diet

Phytic acid forms insoluble complexes with nutritionally essential minerals, including zinc (Zn). Animal studies show that addition of microbial phytase (P) to low-Zn diets improves Zn status and bone strength. The present study determined the effects of phytase supplementation on bone mineral density (BMD), body composition and voluntary running activity of male rats fed a high phytic acid, low-Zn diet. In a factorial design, rats were assigned to ZnLO (5 mg/kg diet), ZnLO+P (ZnLO diet with 1500 U phytase/kg) or ZnAD (30 mg/kg diet) groups and were divided into voluntary exercise (EX) or sedentary (SED) groups, for 9 weeks. SED rats were significantly heavier from the second week, and no catch-up growth occurred in EX rats. Feed intakes were not different between groups throughout the study. ZnLO animals had decreased food efficiency ratios compared to both phytase-supplemented (ZnLO+P) and Zn-adequate (ZnAD) animals ( P<.01 compared to ZnLO). The ZnLO+P and ZnAD rats ran 56–75 km more total distance than ZnLO rats ( P<.05), with the ZnLO+P rats running more kilometers per week than the ZnLO rats by Week 6. In vivo DEXA analyses indicate that rats fed phytase-supplemented diets had higher lean body mass (LBM) than those fed ZnLO diets; and that rats fed the Zn-adequate diets had the highest LBM. Body fat (%) was significantly lower in EX rats and was both Zn- and phytase insensitive. Rats fed phytase-supplemented diets had higher bone mineral content (BMC), bone area (BA) and BMD than rats fed ZnLO diets; and in rats fed ZnAD diets these indices were the highest. The dietary effects on BMC, BA and BMD were independent of activity level. We conclude that consuming supplemental dietary phytase or dietary Zn additively enhances Zn status to increase BMD, LBM and voluntary physical activity in rats fed a low-Zn diet. While the findings confirm that bone health is vulnerable to disruption by moderate Zn deficiency in rats, this new data suggests that if dietary Zn is limiting, supplemental phytase may have beneficial effects on LBM and performance activity.

Forced, Not Voluntary, Exercise Improves Motor Function in Parkinson's Disease Patients

Background. Animal studies indicate forced exercise (FE) improves overall motor function in Parkinsonian rodents. Global improvements in motor function following voluntary exercise (VE) are not widely reported in human Parkinson's disease (PD) patients. Objective. The aim of this study was to compare the effects of VE and FE on PD symptoms, motor function, and bimanual dexterity. Methods. Ten patients with mild to moderate PD were randomly assigned to complete 8 weeks of FE or VE. With the assistance of a trainer, patients in the FE group pedaled at a rate 30% greater than their preferred voluntary rate, whereas patients in the VE group pedaled at their preferred rate. Aerobic intensity for both groups was identical, 60% to 80% of their individualized training heart rate. Results. Aerobic fitness improved for both groups. Following FE, Unified Parkinson's Disease Rating Scale (UPDRS) motor scores improved 35%, whereas patients completing VE did not exhibit any improvement. The control and coordination of grasping forces during the performance of a functional bimanual dexterity task improved significantly for patients in the FE group, whereas no changes in motor performance were observed following VE. Improvements in clinical measures of rigidity and bradykinesia and biomechanical measures of bimanual dexterity were maintained 4 weeks after FE cessation. Conclusions. Aerobic fitness can be improved in PD patients following both VE and FE interventions. However, only FE results in significant improvements in motor function and bimanual dexterity. Biomechanical data indicate that FE leads to a shift in motor control strategy, from feedback to a greater reliance on feedforward processes, which suggests FE may be altering central motor control processes.

管理栄養士の視点からの運動と食生活―現状と今後への教育―

In importance of physical activity and daily exercise has been emphasized for the prevention of lifestyle-related disease. In this review, I would like to discuss the significance of the exercise in young and elderly women.1) Long-distance runners (n=8) and sedentary lifestyle female students (n=19) were enrolled for the study to improve their lifestyle. After assessing the health conditions, they were divided into three groups ; long-distance runner or athlete group (n=8), forced exercise group (n=9), and voluntary exercise group (n=10). In the sedentary group students, waist circumference, resting heart rate and LDL-cholesterol all improved after the trial, suggesting that daily exercise is effective for the promotion of health in young female students.2) In healthy elderly women, the physical strength, number of walking steps, and bone density were followed for 10 years. During the period, body weight slightly decreased ; body height, group power, respiratory function, number of walking steps, basal metabolic rate, amount of exercise, and total energy expenditure were all significantly decreased. Bone density significantly decreased after 5 years. In elderly women, voluntary, active and continuous exercise is good for the conditioning of the daily life, delaying the functional declining although the physical strength was mostly affected by the aging.

Prepubertal physical activity up-regulates estrogen receptor β, BRCA1 and p53 mRNA expression in the rat mammary gland

Findings in BRCA1 mutation carriers suggest that physical activity, particularly during childhood, may be linked to a reduced risk of developing breast cancer. We investigated whether physical activity at puberty alters the expression of BRCA1 and two other tumor suppressor genes--p53 and estrogen receptor (ER)-beta--in rats. In addition, the effects on ER-alpha expression, mammary proliferation and functional epithelial differentiation were investigated as markers of altered mammary cancer risk in rats exposed to regular physical activity at puberty. Female Sprague Dawley rat pups were randomized to voluntary exercise, sham-exercise control and non-manipulated control groups. Treadmill training (20-25 m/min, 15% grade, 30 min/day, 5 days/week) started on postnatal day 14 and continued through day 32. Third thoracic mammary glands (n = 5 per group and age) were obtained at days 32, 48 and 100 and assessed for changes in morphology through wholemounts, and at 100 days cell proliferation by using Ki67 staining, protein levels of ER-alpha and ER-beta by immunohistochemistry, and mRNA expression levels of BRCA1, p53, ER-alpha and ER-beta by real-time PCR. Mammary glands of rats exposed to exercise during puberty contained fewer terminal end buds (TEBs) and a higher number of differentiated alveolar buds and lobules than the sham controls. However, cell proliferation was not significantly altered among the groups. ER-alpha protein levels were significantly reduced, while ER-beta levels were increased in the mammary ducts and lobular epithelial structures of 100-day old rays which were voluntarily exercised at puberty, compared to sham controls. ER-beta, BRCA1 and p53 mRNA levels were significantly higher in the mammary glands of 100-day-old exercised versus sham control rats. Pubertal physical activity reduced mammary epithelial targets for neoplastic transformation through epithelial differentiation and it also up-regulated tumor suppressor genes BRCA1, p53 and ER-beta, and reduced ER-alpha/ER-beta ratio in the mammary gland. It remains to be determined whether the up-regulation of BRCA1, and perhaps p53, explains the protective effect of childhood physical activity against breast cancer in women who carry a germline mutation in one of the BRCA1 alleles.

Phytase supplementation increases food efficiency ratios, performance activity and body composition in rats fed a low zinc diet

Phytic acid forms insoluble complexes with nutritionally essential minerals, including Zn. Addition of microbial phytase to low Zn diets improves Zn status and bone strength. The present study aimed to observe effects of phytase supplementation on food efficiency ratios (FER), body composition and activity in rats fed a high phytic acid, low Zn diet. Rats (n=72) were fed moderately Zn‐deficient (5ppm) diets either with (ZnLO+P) or without (ZnLO) 1,500U phytase/kg, or a Zn‐adequate (30ppm, ZnAD) diet for 9‐weeks, and were divided into voluntary exercise (EX) or sedentary (SED) groups, in a 3x2 design. Both phytase‐ and Zn‐supplementation increased the FER (P&lt;0.01 compared to ZnLO). The ZnLO+P and ZnAD rats ran 56–75 km more distance than ZnLO rats (ns), with the ZnLO+P rats running more km/week (P&lt;0.05) than the ZnLO rats by week 6. In vivo DXA analyses indicated significant phytase (P&lt;0.01) and activity (P&lt;0.02) effects on bone area (BA), but these effects were independent of each other. Zn‐supplementation of ZnLO diets increased BA, BMC and BMD, irrespective of activity. Voluntary running rats exhibit decreased BA and BMC, regardless of diet. Body fat (%) was reduced and lean body mass (%) was increased in EX rats, but neither was influenced by Zn‐ or phytase‐supplementation. This data suggest that if dietary Zn is limiting, supplemental phytase may have beneficial effects on FER, performance activity and body composition.

Brain Damage After Preischemic Locomotor Activity

Back to table of contents Previous article LETTERFull AccessBrain Damage After Preischemic Locomotor ActivityBurak Yulug M.D.,Mustafa Bakar M.D.Erol Ozan M.D.,Burak Yulug M.D.Search for more papers by this author,Mustafa Bakar M.D.Search for more papers by this authorErol Ozan M.D.Search for more papers by this author,Published Online:1 Jan 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A large body of evidence indicates that locomotor activity can be beneficial in maintaining and even improving neural function following insult or disease. 1 It has already been shown, however, that physical exercise can preserve cognitive function in elderly populations, promote functional recovery after CNS traumatic injury, and induce neurogenesis in the adult CNS. 1 Previous studies indicated the protective role of preischemic locomotor activity on neuronal damage after transient cerebral ischemia which involved an enhanced postischemic reperfusion phase. 2 , 3 In order to eliminate the postischemic enhanced reperfusion phase, which may be the consequence of attenuated thromboxane liberation after transient ischemia, we linked exercise with neuronal damage before permanent cerebral ischemia and evaluated the possible neuroprotective effect through 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Adult male C57BL/6j mice (21–25g) were housed in a 12/12 hour light/dark vivarium with ad lib access to food and water and were assigned randomly to a voluntary exercise group or a sedentary control group. The freely-moving mice were exposed to running in a polyethylene cage (30×40×20 cm) equipped with a running wheel for 14 days, which was recorded continuously by a computer. After 14 days of preischemic locomotor activity, the animals were exposed to the permanent focal cerebral ischemia of the middle cerebral artery using an intraluminal filament technique. 4 The rectal temperature was maintained between 36.5 and 37.0°C using a feedback-controlled heating system. The cerebral blood flow was measured by Laser Doppler Flowmetry (LDF), which was declined as to ∼15% of preischemic control levels immediately after thread insertion in all animal groups ( Figure 1 ). The area of infarction was measured by 2% 2,3,5- triphenyltetrazolium chloride staining. FIGURE 1. Laser Doppler Flow Measurements above Middle Cerebral Artery Territory during Permanent Intraluminal Thread Occlusion by Running and Nonrunning AnimalsNo differences in LDF values are detected between animal groups. Values are means ±S.D. In prior studies using the transient ischemia model, it was shown that physical activity protects against ischemic stroke via mechanisms related either to the upregulation of endothelial nitric oxide synthase (eNOS) or to decreased tromboxan A2 in the vasculature. 2 , 3 In contrast, it has been shown that physical exercise can also increase the production of mRNA for neurotrophins and promotes angiogenesis in response to motor exercise. 5 In our study the difference of the infarct volumes between the runner and nonrunner groups was not statistically significant ( Figure 2 ) (64±13 vs. 59±20) (p>0.05, independent samples t test). FIGURE 2. Infarct Volumes of Mice Subjected to Permanent Cerebral Ischemia. Animals Exposed to Preischemic Wheel Running and Control Animals.Note that preischemic locomotor activity leads to a decrease in infarct size which did not reach statistically significance (p>0.05). Data are given as mean±S.D.)This study demonstrates in a well-characterized animal model that the protective effect of regular physical activity by permanent cerebral ischemia is not efficiaous as in transient cerebral ischemia. Although we cannot completely rule out a neuroprotective effect on ischemic episode, our study suggests that a major neuroprotection is conferred during reperfusion by transient ischemia for mice that have undergone exercise preconditioning. This may indicate that reduction of ischemic brain injury may relate more to the augmentation of regional cerebral blood flow (rCBF) than the production of endogen neurotrophins and suggest the protective role of vascular factors rather than parancimal factors by preischemic locomotor activity.However, further studies showing a causal relationship between exercise-induced neural tolerance, cellular expression of neurotrophins, and angiogenesis factors for both models of cerebral ischemia are needed.Department of Neurology, University Hospital Uludag, BursaDepartment of Psychiatry, University of Atatürk, ErzurumReferences1 . Cotman CW, Berchtold NC: Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25:295–301Google Scholar2 . Stummer W, Baethmann A, Murr R, et al: Cerebral protection against ischemia by locomotor activity in gerbils: underlying mechanisms. Stroke 1995; 26:1423–1429Google Scholar3 . Endres M, Gertz K, Lindauer U, et al: Mechanisms of stroke protection by physical activity. Ann Neurol 2003; 54:582–590Google Scholar4 . Kilic E, Dietz PH, Hermann DM, et al: Intravenous TAT-Bcl-XL is protective after middle cerebral artery occlusion in mice. Ann Neurol 2002; 52:617–622Google Scholar5 . Ding Y, Li J, Luan X, et al: Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience 2004; 124:583–591Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 20Issue 1 Winter, 2008Pages 123-124 Metrics PDF download History Published online 1 January 2008 Published in print 1 January 2008

Forced, not voluntary, exercise effectively induces neuroprotection in stroke

Previous treadmill exercise studies showing neuroprotective effects have raised questions as to whether exercise or the stress related to it may be key etiologic factors. In this study, we examined different exercise regimens (forced and voluntary exercise) and compared them with the effect of stress-only on stroke protection. Adult male Sprague-Dawley rats (n = 65) were randomly assigned to treatment groups for 3 weeks. These groups included control, treadmill exercise, voluntary running wheel exercise, restraint, and electric shock. Levels of the stress hormone, corticosterone, were measured in the different groups using ELISA. Animals from each group were then subjected to stroke induced by a 2-h middle cerebral artery (MCA) occlusion followed by 48-h reperfusion. Infarct volume was determined in each group, while changes in gene expression of stress-induced heat shock proteins (Hsp) 27 and 70 were compared using real-time PCR between voluntary and treadmill exercise groups. The level of corticosterone was significantly higher in both stress (P < 0.05) and treadmill exercise (P < 0.05) groups, but not in the voluntary exercise group. Infarct volume was significantly reduced (P < 0.01) following stroke in rats exercised on a treadmill. However, the amelioration of damage was not duplicated in voluntary exercise, even though running distance in the voluntary exercise group was significantly (P < 0.01) longer than that of the forced exercise group (4,828 vs. 900 m). Furthermore, rats in the electric shock group displayed a significantly increased (P < 0.01) infarct volume. Expression of both Hsp 27 and Hsp 70 mRNA was significantly increased (P < 0.01) in the treadmill exercise group as compared with that in the voluntary exercise group. These results suggest that exercise with a stressful component, rather than either voluntary exercise or stress alone, is better able to reduce infarct volume. This exercise-induced neuroprotection may be attributable to up-regulation of stress-induced heat shock proteins 27 and 70.

Brain Damage After Preischemic Locomotor Activity

Back to table of contents Previous article LETTERFull AccessBrain Damage After Preischemic Locomotor ActivityBurak Yulug M.D.,Mustafa Bakar M.D.Erol Ozan M.D.,Burak Yulug M.D.Search for more papers by this author,Mustafa Bakar M.D.Search for more papers by this authorErol Ozan M.D.Search for more papers by this author,Published Online:1 Jan 2008AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A large body of evidence indicates that locomotor activity can be beneficial in maintaining and even improving neural function following insult or disease. 1 It has already been shown, however, that physical exercise can preserve cognitive function in elderly populations, promote functional recovery after CNS traumatic injury, and induce neurogenesis in the adult CNS. 1 Previous studies indicated the protective role of preischemic locomotor activity on neuronal damage after transient cerebral ischemia which involved an enhanced postischemic reperfusion phase. 2 , 3 In order to eliminate the postischemic enhanced reperfusion phase, which may be the consequence of attenuated thromboxane liberation after transient ischemia, we linked exercise with neuronal damage before permanent cerebral ischemia and evaluated the possible neuroprotective effect through 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Adult male C57BL/6j mice (21–25g) were housed in a 12/12 hour light/dark vivarium with ad lib access to food and water and were assigned randomly to a voluntary exercise group or a sedentary control group. The freely-moving mice were exposed to running in a polyethylene cage (30×40×20 cm) equipped with a running wheel for 14 days, which was recorded continuously by a computer. After 14 days of preischemic locomotor activity, the animals were exposed to the permanent focal cerebral ischemia of the middle cerebral artery using an intraluminal filament technique. 4 The rectal temperature was maintained between 36.5 and 37.0°C using a feedback-controlled heating system. The cerebral blood flow was measured by Laser Doppler Flowmetry (LDF), which was declined as to ∼15% of preischemic control levels immediately after thread insertion in all animal groups ( Figure 1 ). The area of infarction was measured by 2% 2,3,5- triphenyltetrazolium chloride staining. FIGURE 1. Laser Doppler Flow Measurements above Middle Cerebral Artery Territory during Permanent Intraluminal Thread Occlusion by Running and Nonrunning AnimalsNo differences in LDF values are detected between animal groups. Values are means ±S.D. In prior studies using the transient ischemia model, it was shown that physical activity protects against ischemic stroke via mechanisms related either to the upregulation of endothelial nitric oxide synthase (eNOS) or to decreased tromboxan A2 in the vasculature. 2 , 3 In contrast, it has been shown that physical exercise can also increase the production of mRNA for neurotrophins and promotes angiogenesis in response to motor exercise. 5 In our study the difference of the infarct volumes between the runner and nonrunner groups was not statistically significant ( Figure 2 ) (64±13 vs. 59±20) (p>0.05, independent samples t test). FIGURE 2. Infarct Volumes of Mice Subjected to Permanent Cerebral Ischemia. Animals Exposed to Preischemic Wheel Running and Control Animals.Note that preischemic locomotor activity leads to a decrease in infarct size which did not reach statistically significance (p>0.05). Data are given as mean±S.D.)This study demonstrates in a well-characterized animal model that the protective effect of regular physical activity by permanent cerebral ischemia is not efficiaous as in transient cerebral ischemia. Although we cannot completely rule out a neuroprotective effect on ischemic episode, our study suggests that a major neuroprotection is conferred during reperfusion by transient ischemia for mice that have undergone exercise preconditioning. This may indicate that reduction of ischemic brain injury may relate more to the augmentation of regional cerebral blood flow (rCBF) than the production of endogen neurotrophins and suggest the protective role of vascular factors rather than parancimal factors by preischemic locomotor activity.However, further studies showing a causal relationship between exercise-induced neural tolerance, cellular expression of neurotrophins, and angiogenesis factors for both models of cerebral ischemia are needed.Department of Neurology, University Hospital Uludag, BursaDepartment of Psychiatry, University of Atatürk, ErzurumReferences1 . Cotman CW, Berchtold NC: Exercise: a behavioral intervention to enhance brain health and plasticity. Trends Neurosci 2002; 25:295–301Google Scholar2 . Stummer W, Baethmann A, Murr R, et al: Cerebral protection against ischemia by locomotor activity in gerbils: underlying mechanisms. Stroke 1995; 26:1423–1429Google Scholar3 . Endres M, Gertz K, Lindauer U, et al: Mechanisms of stroke protection by physical activity. Ann Neurol 2003; 54:582–590Google Scholar4 . Kilic E, Dietz PH, Hermann DM, et al: Intravenous TAT-Bcl-XL is protective after middle cerebral artery occlusion in mice. Ann Neurol 2002; 52:617–622Google Scholar5 . Ding Y, Li J, Luan X, et al: Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin. Neuroscience 2004; 124:583–591Google Scholar FiguresReferencesCited byDetailsCited byNone Volume 20Issue 1 Winter, 2008Pages 123-124 Metrics PDF download History Published online 1 January 2008 Published in print 1 January 2008

Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle

Voluntary exercise (VE) has a beneficial influence on the heart and mean lifespan. The present study evaluates structural adaptations of cardiomyocytes and their mitochondria due to VE by new, unbiased stereological methods. Female, 7-9-week-old mice were randomly assigned to a control (CG, n = 7) or VE group (EG, n = 7). EG animals were housed in cages with free access to a running wheel and had a mean running distance of 6.7 (1.8) km per day. After 4 weeks, the hearts of all mice were processed for light and electron microscopy. We estimated the number and volume of cardiomyocytes by the disector method and the number and volume of mitochondria by estimation of the Euler number. In comparison to CG, VE did not have an effect on the myocardial volume of the left ventricle (CG: 93 (10), EG: 103 (17) (mm(3))), the number of cardiomyocytes (CG: 2.81 (0.27), EG: 2.82 (0.43) (x10(6))) and their number-weighted mean volume. However, the composition of the cardiomyocytes changed due to VE. The total volume of mitochondria (CG: 21.8 (4.9), EG: 32.2 (4.3) (mm(3)), P < 0.01) and the total number (CG: 3.76 (0.44), EG: 7.02 (1.13) (x10(10)), P < 0.001) were significantly higher in EG than in CG. The mean number-weighted mitochondrial volume was smaller in EG than in CG (P < 0.05). In summary, VE does not alter ventricular volume nor cardiomyocyte volume or number but the oxidative capacity of cardiomyocytes by an increased mitochondrial number and total volume in the left ventricle. These structural changes may participate in the beneficial effects of VE.

Effects of different types of physical exercise on the staining of parvalbumin-positive neurons in the hippocampal formation of rats with epilepsy

Effects of exercise in animals with epilepsy have been demonstrated. To investigate whether the type of physical activity, voluntary or forced, would promote different morphological changes in hippocampal formation we performed an immunocytochemical study using the parvalbumin (PV) distribution as a marker. Control rats and rats with epilepsy were submitted to a voluntary (wheel running) and forced (treadmill) exercise for 10 days (acute physical exercise) or 45 days (chronic physical exercise). It was observed in normal rats a higher number of PV-positive cells in the hilus of dentate gyrus (DG) in the voluntary and forced exercise groups (acute and chronic physical exercise), when compared to the control group. In animals with epilepsy the number of PV-positive cells and staining intensity of PV-fibers in the hilus was significantly higher only in the acute physical exercise (voluntary and forced). These findings demonstrate that acute physical exercise, both voluntary and forced results in increased number of PV-positive cells and staining intensity of PV-fibers in the hilus of rats with epilepsy and the occurrence of these changes takes place only in the early phase of epilepsy.

Voluntary wheel-running exercise enhances antigen-specific antibody-producing splenic B cell response and prolongs IgG half-life in the blood

Exercise has been recognized to provoke upregulation of antibodies. However, the mechanism has not been explained. We examined the effects of voluntary wheel-running exercise on the number of cells which produce tetanus toxoid (TT)-specific IgG, as well as serum level and clearance of administered 125I-labeled mouse IgG in the blood. Male C57BL/6N mice were randomly divided into a voluntary wheel-running exercise group and a sedentary group. Mice were intraperitoneally immunized with 0.375 microg/kg of TT to induce primary and secondary anti-TT antibody responses. ELISPOT assays that identified TT-specific antibody production were performed on day 0 (Baseline, n = 8) and 22 (EX: n = 8, Non-EX: n = 8) after initial immunization (primary response) and on day 32 (EX: n = 8, Non-EX: n = 7) and 43 (EX: n = 7, Non-EX: n = 7). To explain why serum TT-specific IgG was elevated in the exercise group, we conducted an 125I-labeled mouse IgG clearance test on day 32. ELISPOT counts of secondary responses to TT immunization were significantly higher in the running group than in the sedentary group (P<0.05). The serum anti-TT specific IgG concentration was also significantly higher in the running group (P<0.05) than in the sedentary on day 32. The values of both groups were relatively lower on day 43. The (125)I-labeled mouse IgG was more rapidly cleared in the non-exercised than in the exercised group (P<0.05). These results show that voluntary wheel running upregulates the TT-specific humoral immune response. These reactions may be partly explained by the accelerated induction of TT-specific IgG-producing cells and prolonged serum IgG half-life with voluntary exercise.

Voluntary Wheel Running In Rats Receiving Doxorubicin

The chemotherapy drug doxorubicin (DOX) is effective at combating cancerous cell growth and proliferation, but its dosing is limited because chronic usage can result in cardiac dysfunction with eventual heart failure. Previously, we have shown that endurance training prior to DOX administration ameliorates DOX-induced cardiac dysfunction which translates into improved DOX-tolerance in a trained organism. However, the likelihood of training during DOX treatment to prevent cardiac maladaptation has yet to be explored. Additionally, it has been shown that DOX treatment promotes a shift in cardiac myosin heavy chain (MHC) expression from the fast á-isoform to the slow â-isoform. PURPOSE To analyze the effects of voluntary wheel running on cardiac MHC composition in rats receiving DOX. METHODS Female Sprague-Dawley rats were randomly assigned to the voluntary running (n = 9) or the sedentary (n = 8) group. Following a 2-week running wheel acclimation period, animals received weekly IP injections of DOX (2.5 mg/kg) for 6 weeks. The voluntary running group had access to running wheels throughout the treatment period. Following 6 weeks of DOX, left ventricular free walls from the animals were analyzed for MHC composition using SDS-PAGE. RESULTS The week prior to DOX injections, the rats ran a mean of 10.4±5.1 km/ day, and following week 3 of DOX, animals ran a mean of 6.7±3.8 km/day (36% decrease). Following 6 weeks of treatment, animals ran a mean of 4.1±3.0 km/day (61% decrease). The voluntary exercise group expressed a mean á-MHC percentage of 75.5±9.9% which was significantly greater than the mean á-MHC percentage of 56.8±18.5% detected in sedentary animals (p = 0.01). CONCLUSIONS Increased physical activity during DOX treatment preserved contractile MHC isoform distribution in the left ventricle. This suggests that increased physical activity during DOX treatment may help protect the heart from cardiac dysfunction.

Differential effects of spontaneous versus forced exercise in rats on the staining of parvalbumin-positive neurons in the hippocampal formation

To investigate whether the type of physical activity, voluntary or forced, would promote different morphological changes in hippocampal formation we performed an immunocytochemical study using the parvalbumin (PV) distribution as a marker. Animals submitted to the voluntary exercise were placed in a voluntary wheel running and those submitted to the forced exercise were placed in a motor driven treadmill. Both exercise groups were submitted to 10 consecutive days of physical activity. It was observed a higher number of PV-positive cells in the hilus of dentate gyrus (DG) in the voluntary and forced exercise groups when compared to the control group. The voluntary exercise group also presented a stronger fiber staining in the DG hilus than the forced exercise and control groups. In contrast, no differences were found in the pattern of PV staining in CA1/CA3 region between exercise and control groups. These findings demonstrate that physical activity leads to prominent plastic changes in the hippocampal formation of rats that were more evident following voluntary activity.

Assessment of training effects on activity levels of alveolar macrophage in matured rats using chemiluminescent technique.

Chemiluminescence responses have been used for the evaluation of phagocyte function. In this study, to evaluate effects of training started after maturation on pulmonary immunity, the activity levels of rat alveolar macrophages (AMs) were assessed as reactive oxygen species (ROS) generating capacity, measured by lucigenin- and luminol-dependent chemiluminescence, using a parallel luminometer. One group of male Wistar rats started training at 11 weeks old and another group at 17 weeks old. The experimental period was 12 weeks, and about half of the rats were sacrificed after 6 weeks. The forced and voluntary exercises affect the mean levels of body weights and cell populations in the bronchoalveolar lavage fluid in younger animals; however, the voluntary exercise group in younger animals seemed to adapt after 12 weeks. By contrast, chemiluminescence responses in older rats observed after 6 weeks suggest that AMs are primed, and the maximum releasing activities of ROS are reduced. These changes in AM activity may be caused by the exercise and separation stresses and the rats may adapt to those stressors after 12 weeks. The chemiluminescent technique is thought to be useful to evaluate the changes of AM activity.

Effects of voluntary running exercise on blood pressure and renin-angiotensin system in spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

The effect of a voluntary running exercise on blood pressure and renin-angiotensin system (RAS) was studied in male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). SHR and WKY were assigned to either voluntary running exercise or sedentary control groups at 5 wk of age. The systolic blood pressure in the exercised group for both strains of rats was significantly lower than in the sedentary control group. The plasma renin activity (PRA) and plasma renin concentration (PRC) were significantly lower in voluntary running exercised SHR than in sedentary SHR, whereas the same exercise did not result in a lower PRA and PRC in WKY. These results suggested that the blood pressure lowering effect of voluntary running exercise is related to the suppression of RAS in SHR.

Geometrical, Mechanical, and Structural Adaptation of Mouse Femora Exposed to Different Loadings

Juvenile mice were utilized as a model system to study the influence of different activity regimens on the change in bone morphology and load-bearing capacity of their femora. Two treatment groups were employed: one exposed to 4g hypergravity (HG) and the other to chronic digging in high ground corn cob litter (HL). A voluntary normal exercise group (NE) served as control. One femur from each animal was used to determine the geometrical properties of the bone; the other femur was used in a load-to-failure experiment. Electron micrographs of femur cross sections were digitized to yield geometrical properties of the bone. Young's modulus and the stress and strain at failure for the bone were determined via a modified Euler beam model. Strain energy was evaluated directly from load-deflection curves obtained during the load-to-failure experiments. Average strain-energy density was then derived from these results. Cross-sectional geometrical properties (diameters, wall thicknesses, area, moments of inertia, a...

Natural immunity and chronic exercise in rats. The involvement of the spleen and the splenic nerves

We have previously shown that voluntary running for 4–5 weeks in the spontaneously hypertensive rat (SHR) significantly increased in natural cytotoxic mechanism in vivo, measured as clearance of 51Cr YAC-1 lymphoma cells from the lungs. In the present study, we have studied the possible role of the spleen and the splenic nerves in this augmentation. The SHR were randomly allocated to either a voluntary exercise group or a sedentary control group. After four weeks of exercise the runners and sedentary control SHR were further assigned to one of four groups: 1) no surgery, 2) sham operation, 3) splenic nerve section and 4) splenectomy. Splenectomy drastically reduced in vivo cytotoxicity in both runners and sedentary controls, but in vivo cytotoxicity of splenectomized voluntary runners was significantly higher than that of splenectomized sedentary control animals. Selective denervation of the spleen did not affect the in vivo cytotoxicity. These results indicate that the enhanced in vivo natural cytotoxic mechanism following voluntary chronic exercise in SHR is partly dependent on intact splenic function. However, this enhancement does not seem to be mediated by the splenic sympathetic nerves.

Effects of voluntary exercise on bone growth and calcium metabolism in spontaneously hypertensive rats.

The effects of voluntary exercise on bone length and calcium metabolism were investigated in spontaneously hypertensive rats (SHR) and Wistar rats. They were classified into voluntary exercise or sedentary group. Systolic blood pressure (SBP), bone length, urinary calcium excretion, plasma calcium and parathyroid hormone levels (PTH) were measured for analysis. SBP of the trained SHR (T-SHR) was significantly lower than that of the nontrained SHR (NT-SHR) at 10 and 11 weeks of age, but the trained Wistar rats (T-WR) and the nontrained Wistar rats (NT-WR) had similar SBP throughout the experimental period. The T-SHR had significantly longer bones in the extremities and the trunk than the NT-SHR, whereas the T-WR had similar or shorter bones than the NT-WR. The PTH level at 12 weeks of age was significantly lower in the T-SHR than in the NT-SHR. The urinary calcium excretion of the T-SHR was greater than that of the NT-SHR, but the food intake (calcium intake) of the T-SHR was also greater. The urinary calcium excretion and food intake of the T-WR and NT-WR were similar. No noticeable differences were observed in the plasma calcium level between the T-SHR and NT-SHR, the T-WR and NT-WR. From these results it is suggested that the abnormal calcium metabolism in the SHR is improved in some degree by voluntary exercise.

Neuromuscular electrical stimulation. An overview and its application in the treatment of sports injuries.

In sports medicine, neuromuscular electrical stimulation (NMES) has been used for muscle strengthening, maintenance of muscle mass and strength during prolonged periods of immobilisation, selective muscle retraining, and the control of oedema. A wide variety of stimulators, including the burst-modulated alternating current ('Russian stimulator'), twin-spiked monophasic pulsed current and biphasic pulsed current stimulators, have been used to produce these effects. Several investigators have reported increased isometric muscle strength in both NMES-stimulated and exercise-trained healthy, young adults when compared to unexercised controls, and also no significant differences between the NMES and voluntary exercise groups. It appears that when NMES and voluntary exercise are combined there is no significant difference in muscle strength after training when compared to either NMES or voluntary exercise alone. There is also evidence that NMES can improve functional performance in a variety of strength tasks. Two mechanisms have been suggested to explain the training effects seen with NMES. The first mechanism proposes that augmentation of muscle strength with NMES occurs in a similar manner to augmentation of muscle strength with voluntary exercise. This mechanism would require NMES strengthening protocols to follow standard strengthening protocols which call for a low number of repetitions with high external loads and a high intensity of muscle contraction. The second mechanism proposes that the muscle strengthening seen following NMES training results from a reversal of voluntary recruitment order with a selective augmentation of type II muscle fibres. Because type II fibres have a higher specific force than type I fibres, selective augmentation of type II muscle fibres will increase the overall strength of the muscle. The use of neuromuscular electrical stimulation to prevent muscle atrophy associated with prolonged knee immobilisation following ligament reconstruction surgery or injury has been extensively studied. NMES has been shown to be effective in preventing the decreases in muscle strength, muscle mass and the oxidative capacity of thigh muscles following knee immobilisation. In all but one of the studies, NMES was shown to be superior in preventing the atrophic changes of knee immobilisation when compared to no exercise, isometric exercise of the quadriceps femoris muscle group, isometric co-contraction of both the hamstrings and quadriceps femoris muscle groups, and combined NMES-isometric exercise. It has also been reported that NMES applied to the thigh musculature during knee immobilisation improves the performance on functional tasks.(ABSTRACT TRUNCATED AT 400 WORDS)