Daily Running Distance Research Articles

Changes in mRNA levels for brain-derived neurotrophic factor after wheel running in rats selectively bred for high- and low-aerobic capacity

We evaluated levels of exercise-induced brain-derived neurotrophic factor (BDNF) messenger RNA (mRNA) within the hippocampal formation in rats selectively bred for 1) high intrinsic (i.e., untrained) aerobic capacity (High Capacity Runners, HCR), 2) low intrinsic aerobic capacity (Low Capacity Runners, LCR), and 3) unselected Sprague–Dawley (SD) rats with or without free access to running wheels for 3weeks. The specific aim of the study was to determine whether a dose–response relationship exists between cumulative running distance and levels of BDNF mRNA. No additional treatments or behavioral manipulations were used. HCR, LCR, and SD rats were grouped by strain and randomly assigned to sedentary or activity (voluntary access to activity wheel) conditions. Animals were killed after 21days of exposure to the assigned conditions. Daily running distances (mean±standard deviation meters/day) during week three were: HCR (4726±3220), SD (2293±3461), LCR (672±323). Regardless of strain, levels of BDNF mRNA in CA1 were elevated in wheel runners compared to sedentary rats and this difference persisted after adjustment for age (p=0.040). BDNF mRNA was not affected by intrinsic aerobic capacity and was not related to total running distance. The results support that BDNF mRNA expression is increased by unlimited access to activity wheel running for 3weeks but is not dependent upon accumulated running distance.

Adult hippocampal neurogenesis and c-Fos induction during escalation of voluntary wheel running in C57BL/6J mice

Voluntary wheel running activates dentate gyrus granule neurons and increases adult hippocampal neurogenesis. Average daily running distance typically increases over a period of 3 weeks in rodents. Whether neurogenesis and cell activation are greater at the peak of running as compared to the initial escalation period is not known. Therefore, adult C57BL/6J male mice received 5 days of BrdU injections, at the same age, to label dividing cells during the onset of wheel access or after 21 days during peak levels of running or in sedentary conditions. Mice were sampled either 24h or 25 days after the last BrdU injection to measure cell proliferation and survival, respectively. Immunohistochemistry was performed on brain sections to identify the numbers of proliferating BrdU-labeled cells, and new neurons (BrdU/NeuN co-labeled) in the dentate gyrus. Ki67 was used as an additional mitotic marker. The induction of c-Fos was used to identify neurons activated from running. Mice ran approximately half as far during the first 5 days as compared to after 21 days. Running increased Ki67 cells at the onset but after 21 days levels were similar to sedentary. Numbers of BrdU cells were similar in all groups 24h after the final injection. However, after 25 days, running approximately doubled the survival of new neurons born either at the onset or peak of running. These changes co-varied with c-Fos expression. We conclude that sustained running maintains a stable rate of neurogenesis above sedentary via activity-dependent increases in differentiation and survival, not proliferation, of progenitor cells in the C57BL/6J model.

Enforced expression of protein kinase C in skeletal muscle causes physical inactivity, fatty liver and insulin resistance in the brain

Among the multitude of dysregulated signalling mechanisms that comprise insulin resistance in divergent organs, the primary events in the development of type 2 diabetes are not well established. As protein kinase C (PKC) activation is consistently present in skeletal muscle of obese and insulin resistant subjects, we generated a transgenic mouse model that overexpresses constitutively active PKC-β2 in skeletal muscle to test whether activation of PKC is sufficient to cause an aversive whole-body phenotype. Upon this genetic modification, increased serine phosphorylation in Irs1 was observed and followed by impaired 3H-deoxy-glucose uptake and muscle glycogen content, and transgenic mice exhibited insulin and glucose intolerance as they age. Muscle histochemistry revealed an increase in lipid deposition (intramyocellular lipids), and transgenic mice displayed impaired expression of transcriptional regulators of genes involved in fatty acid oxidation (peroxisome proliferator-activated receptor-γ, PGC-1β, acyl-CoA oxidase) and lipolysis (hormone-sensitive lipase). In this regard, muscle of transgenic mice exhibited a reduced capacity to oxidize palmitate and contained less mitochondria as determined by citrate synthase activity. Moreover, the phenotype included a profound decrease in the daily running distance, intra-abdominal and hepatic fat accumulation and impaired insulin action in the brain. Together, our data suggest that activation of a classical PKC in skeletal muscle as present in the pre-diabetic state is sufficient to cause disturbances in whole-body glucose and lipid metabolism followed by profound alterations in oxidative capacity, ectopic fat deposition and physical activity.

Elevated IL‐1RA levels blunt exercise‐induced increases in Hsp25 and Hsp72 in mouse muscle

Evidence using heat or transgenic up‐regulation of heat shock proteins (Hsp)72 and 25 suggest they may protect against obesity‐induced insulin resistance. We reported that running wheel training significantly increased Hsp72 and Hsp25 in active muscles of lean mice suggesting their contribution to improved glucose regulation with exercise. However, obesity is associated with higher levels of circulating IL‐1 receptor antagonist (IL‐1RA) that may impact Hsp up‐regulation. We tested the hypothesis that high IL‐1RA levels blunt exercise‐induced Hsp up‐regulation in muscle by blocking the actions of IL‐1. We compared Hsp72 and Hsp25 protein levels with Western blot in muscle of C57 mice (n=4/group) following 3 days of wheel running ± Kineret® (KIN), a recombinant IL‐1RA. Exercise increased Hsp25 and Hsp 72 protein from 0.08±0.02 to 0.16±0.03 and 0.10±0.04 to 0.19±0.03 arbitrary units in saline groups, respectively. No changes in either Hsp were seen with exercise and KIN. Average daily wheel running time (4.6±0.5 vs. 4.6±0.4 h) and distance (4.0±0.5 vs. 4.1±0.4 km) was not different between saline and KIN, respectively. These results suggest that high levels of circulating IL‐1RA may attenuate Hsp up‐regulation in active muscles. However, longer‐term training may reduce adiposity which subsequently may decrease circulating IL‐1RA and improve Hsp responses. Funded in part by NIH DK64862 and NS58525 to GGF

Running Behavior and Its Energy Cost in Mice Selectively Bred for High Voluntary Locomotor Activity

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 males might partly explain the apparent selection limit for wheel running observed for over 15 generations.

Decline in Daily Running Distance Presages Disease Onset in a Mouse Model of ALS

Amyotrophic lateral sclerosis (ALS) is characterized by progressive degeneration of lower motor neurons resulting in paralysis and death. Epidemiological and clinical findings suggest that a decline in athletic performance may presage the clinical onset of ALS, but this possibility has not been tested in an animal model. By placing running wheels in each mouse's cage to measure their exercise activity, we show that presymptomatic G93A SOD1 ALS mice are more active runners (15-20 km/day) than control mice (7-9 km/day). The ALS mice then exhibit a sharp decline in daily running distance 10-20 days prior to the onset of clinical disease. Within the group of ALS mice, there were no significant correlations between cumulative lifetime running distance and age at clinical disease onset or age at death, suggesting that amount of exercise did not affect the course of the disease process. Our data show that presymptomatic ALS mice have a propensity for running long distances, and then dramatically reduce the amount they run prior to the appearance of clinical symptoms. The monitoring of voluntary running distance may provide a valuable biomarker to evaluate the efficacy of potential therapeutic interventions for ALS in preclinical studies.

Endurance capacity in maturing mdx mice is markedly enhanced by combined voluntary wheel running and green tea extract

Duchenne muscular dystrophy is characterized by the absence of dystrophin from muscle cells. Dystrophic muscle cells are susceptible to oxidative stress. We tested the hypothesis that 3 wk of endurance exercise starting at age 21 days in young male mdx mice would blunt oxidative stress and improve dystrophic skeletal muscle function, and these effects would be enhanced by the antioxidant green tea extract (GTE). In mice fed normal diet, average daily running distance increased 300% from week 1 to week 3, and total distance over 3 wk was improved by 128% in mice fed GTE. Running, independent of diet, increased serum antioxidant capacity, extensor digitorum longus tetanic stress, and total contractile protein content, heart citrate synthase, and heart and quadriceps beta-hydroxyacyl-CoA dehydrogenase activities. GTE, independent of running, decreased serum creatine kinase and heart and gastrocnemius lipid peroxidation and increased gastrocnemius citrate synthase activity. These data suggest that both endurance exercise and GTE may be beneficial as therapeutic strategies to improve muscle function in mdx mice.

Increased voluntary exercise in mice deficient for tumour necrosis factor‐α and lymphotoxin‐α

The endogenous mediators playing a role in the sensing of fatigue and cessation of exercise are yet to be characterized. We hypothesized that proinflammatory cytokines, in particular tumour necrosis factor-alpha (TNFalpha) and lymphotoxin-alpha (LT) transmit signals leading to fatigue. Mice were placed in a cage with a freely rotating exercise wheel and allowed to adapt for 24 h. The running distance was measured for two additional periods of 24 h. The effects of the administration of intravenous anti-TNF antibodies, intracerebral recombinant TNF, or intravenous lipopolysaccharide (LPS) were also determined. Compared to normal littermates, the voluntary daily running distance was 1.8-fold greater in mice with a disruption of the gene for TNFalpha, and 3-fold greater in mice with a gene disruption for both TNFalpha and LT. Intravenous administration of a monoclonal antibody against murine TNFalpha did not affect the running distance of wild-type mice, whereas administration of TNF intracerebrally reduced by 4-fold the voluntary running distance of the animals. This demonstrates that fatigue is mediated by TNFalpha expressed in the central nervous system (CNS) and not by increased peripheral TNFalpha concentrations. TNFalpha and LT are strong inducers of prostaglandins, but mice with disrupted prostaglandin or prostacyclin receptors exhibited running distances not significantly different from their wild-type littermates. Thus, signalling molecules other than prostaglandins mediate the effect of TNFalpha and LT on exercise capacity. Our finding that exercise capacity is controlled by TNFalpha is the first to define the endogenous mediators of fatigue, and may have important implications for diseases with impaired exercise tolerance.

Voluntary Exercise and the Development of Osteoarthritis in Mice Fed a High-fat Diet

Osteoarthritis (OA) is a progressive, degenerative joint disease characterized by an imbalance of articular cartilage biosynthesis and degradation attributed to both inflammatory and biomechanical factors. Obesity, or factors associated with obesity, are a primary risk factor for OA in both load-bearing and non-load bearing joints, suggesting that systemic factors mediate obesity-induced OA. PURPOSE: To test the hypothesis that voluntary exercise mitigates the development of OA in diet-induced obese mice. METHODS: 12-week old male mice (C57BL/6J) were fed either normal chow (NC) (n = 10) or high-fat (HF) chow (60% kcal fat) (n = 10). After 8 weeks of feeding, half the mice from each diet group were housed in cages equipped with a custom-designed running wheel that allowed for continuous monitoring of voluntary running activity. Mice continued to have free access to their respective diets during the exercise period. The study ended when the mice were 24 weeks old (i.e., after 4 weeks of exercise). Percent body fat was assessed using DEXA analysis. Knee joint degeneration was assessed using histomorphometric analysis following a modified Mankin OA scoring system developed for mice. RESULTS: HF feeding significantly increased body mass (HF: 37.9 ± 1.3 g, NC: 24.4 ± 0.35 g, P < 0.05), percent body fat (HF: 34.7 ± 2.1%, NC: 11.0 ± 0.44%, P < 0.05), and joint degeneration (HF: 18.2 ± 2.4, NC: 10.4 ± 2.1, P < 0.05) in non-exercised mice. Diet, however, did not affect the average daily running distance in exercised mice (HF: 6.15 ± 0.67 km/day, NC: 6.75 ± 0.70 km/day, P = 0.6). Contrary to our hypothesis, exercise did not affect joint degeneration in either the HF (18.2 ± 0.7, P = 0.75) or the NC (12.4 ± 2.0, P = 0.67) fed mice. Body mass and percent body fat were not affected by 4 weeks of voluntary exercise in either diet group. CONCLUSION: High-fat feeding is an effective means of inducing non-traumatic joint degeneration in mice at a relatively young age. Voluntary wheel running exercise did not affect the development of joint degeneration in the medial compartment of the knee joint. Our previous studies of HF diet-induced OA in mice indicate that joint degeneration is positively correlated with body mass and body fat. Thus, longer duration or higher intensity exercise that is sufficient to reduce body mass or fat levels may be needed to alter the pathogenesis of HF diet-induced OA in mice. Supported by NIH grants AR50245 and AR51672.

Effects of long-term creatine feeding and running on isometric functional measures and myosin heavy chain content of rat skeletal muscles

The purpose of this study was to investigate whether creatine (Cr) supplementation during 12 weeks of phasic high-frequency voluntary wheel running would result in a faster myosin heavy chain (MHC) isoform profile in the rat mixed fast-twitch plantaris and alter its corresponding isometric contractile properties. The fast-twitch extensor digitorum longus and medial gastrocnemius and slow-twitch soleus were also studied. Forty weanling Sprague-Dawley male rats were assigned to one of four groups: creatine-sedentary (Cre-Sed); creatine-voluntary running (Cre-Run); control-sedentary (Con-Sed); control-voluntary running (Con-Run). Daily running distance was similar between Cre-Run and Con-Run. Average daily Cr ingestion was also similar being 2.4+/-0.17 and 3.0+/-0.14 g/kg in Cre-Sed and Cre-Run, respectively. Total creatine (TCr) content was elevated (P<0.03) in the plantaris of Cre-Run [211.4+/-16.9 mmol/kg dry weight (dw)], compared with Con-Run (175.1+/-5.69). In the plantaris, MHCIIb was 13% greater (P<0.00001) in Cre-Run compared with Con-Run, while MHCIId/x and MHCIIa were lower in Cre-Run by 7 and 6% (P<0.0002), respectively. No differences were observed in twitch force, time-to-peak tension, half-rise time or half-fall time. Greater tetanic force production (P<0.05) in Cre-Sed compared with Con-Sed corresponded to a 12% increase in MHCIId/x (P<0.0001) and a 12% decrease in MHCIIb (P<0.0006). The fatigue index of the plantaris at 10 s (FI(10s)) was reduced only after running (Cre-Run vs Con-Run), while in all other muscles the FI(10s) was lower only in the Cre-Sed group. In conclusion, Cr supplementation had differential effects on MHC isoform content and fatigability that depended on the level of contractile activity. Cr feeding combined with running exercise resulted in a faster MHC-based phenotype in the rat plantaris but the impact on associated isometric contractile properties was minimal.

Abnormal Response to Physical Activity in Femurs after Heterozygous Inactivation of One Allele of the Col2a1 Gene for Type II Collagen in Mice

The objective of this study was to evaluate the influence of heterozygous inactivation of one allele of the type II collagen gene (Col2a1) on biomechanical properties and mineral density of bone under physical loading conditions. C57BL/6-TGN mice with heterozygous knockout (HZK) inactivation of Col2a1 gene and their nontransgenic littermate controls were housed in individual cages with running wheels for 9 and 15 months. The running activity of each mouse was monitored continuously throughout the experiment. Bone mineral density (BMD) of mice femora was measured using dual-energy X-ray absorptiometry (DXA) and peripheral quantitative computerized tomography (pQCT). Biomechanical properties were determined using three-point bending tests. Vertebral bone samples were prepared for quantitative polarized light microscopy and digital densitometry of proteoglycans. The concentration of total collagen and collagen cross-links were analyzed using high-performance liquid chromatograpy (HPLC). The average daily running distance was shorter for the HZK mice between the age of 4 and 15 months as compared with normal runners (P < 0.05). The ultimate breaking force was 14.8% and 23.6% (9 vs. 15 months) lower in HZK-runners than in wild-type runners. BMD of the femur was 6.1% lower in HZK-runners at the age of 9 months (P < 0.05). Physical activity increased cortical BMD in wild-type runners but not in the HZK runners at the age of 9 months. The collagen network of the HZK mice was less organized. There were only minor changes in BMD and mechanical and structural properties between sedentary HZK mice and their wild-type controls. Increased physical activity induced significantly lower bone density, mechanical properties, and organization of collagen fibers in male HZK mice. However, there were no major differences in biomechanical parameters between sedentary HZK and wild-type male mice. This suggests an important guiding role of collagen type II in bone remodelling and maturation.

Voluntary running distance is negatively correlated with striatal dopamine release in untrained rats

This study examined the relationship between voluntary running distance and glutamate- and K +-stimulated dopamine release in the striatum (nucleus accumbens and caudate-putamen) of male Long–Evans rats. Twenty-one rats were housed individually in cages with attached running-wheels for 1 week. There was a 19-fold variability between rats in voluntary running distances over this period (range=2.3–44.6 km). The average distance completed during the week was 16±2.8 km. There was a strong positive correlation between the running distances completed during the first 24 h (day 1) and the last 24 h. Certain rats were therefore inclined to run from the start. The average daily running distance (2.4±0.4 km per day) was negatively correlated with the weight of the rat ( r=−0.82). Glutamate-stimulated release of dopamine was not a significant predictor of voluntary running distance. However, the average daily running distance was negatively correlated with K +-stimulated dopamine release in the nucleus accumbens core and caudate-putamen but not the nucleus accumbens shell. The present findings suggest that decreased depolarization-induced release of striatal dopamine may be a predictor of hyperactivity. The results show, in a normal population of Long–Evans rats, that there are, at the end of the continuum, rats that display some of the neurochemical and behavioral characteristics of a rat model for attention-deficit hyperactivity disorder.

Voluntary running distance is negatively correlated with striatal dopamine release in untrained rats

This study examined the relationship between voluntary running distance and glutamate- and K + -stimulated dopamine release in the striatum (nucleus accumbens and caudate-putamen) of male Long–Evans rats. Twenty-one rats were housed individually in cages with attached running-wheels for 1 week. There was a 19-fold variability between rats in voluntary running distances over this period (range=2.3–44.6 km). The average distance completed during the week was 16±2.8 km. There was a strong positive correlation between the running distances completed during the first 24 h (day 1) and the last 24 h. Certain rats were therefore inclined to run from the start. The average daily running distance (2.4±0.4 km per day) was negatively correlated with the weight of the rat ( r =−0.82). Glutamate-stimulated release of dopamine was not a significant predictor of voluntary running distance. However, the average daily running distance was negatively correlated with K + -stimulated dopamine release in the nucleus accumbens core and caudate-putamen but not the nucleus accumbens shell. The present findings suggest that decreased depolarization-induced release of striatal dopamine may be a predictor of hyperactivity. The results show, in a normal population of Long–Evans rats, that there are, at the end of the continuum, rats that display some of the neurochemical and behavioral characteristics of a rat model for attention-deficit hyperactivity disorder.

Increased wheel-running activity in the genetically skeletal muscle fast-twitch fiber-dominant rats.

The purpose of the present study was to investigate whether genetic differences in muscle histochemical characteristics were related to the voluntary wheel-running activity level by using genetically fast-twitch fiber-dominant rats (FFDR) and control rats (CR). The rats were divided into four groups; sedentary CR (Sed-CR), wheel-running CR (WR-CR), sedentary FFDR (Sed-FFDR), and wheel-running FFDR (WR-FFDR). Wheel access was started at age 9 wk and lasted for 7 days. The FFDR showed a lower percentage of type I fibers of the deep portion of gastrocnemius and soleus muscles and a higher percentage of both type IIX fibers of the gastrocnemius muscle and type IIA fibers of the soleus muscle compared with CR. A higher capillary density and smaller fiber cross-sectional area were also observed in FFDR. The daily running distance in WR-FFDR was higher than in WR-CR for each 7 days. The total running distance for 7 days in WR-FFDR was 3.2-fold higher than in WR-CR. On day 7 of the 7-day test, the total number of active 1-min intervals for 24 h, the average rpm when they were active, and the maximum rpm for any single 1-min period in the WR-FFDR were significantly higher than in the WR-CR (1.5-, 2.9-, and 2.0-fold, respectively). These results suggest that mechanical or physiological muscle characteristics may thus affect the wheel-running activity level.

Changes in urine 8-hydroxydeoxyguanosine levels of super-marathon runners during a four-day race period

We have determined the urinary 8-hydroxydeoxyguanosine (8-OHdG) levels of five well trained supra-marathon runners during a four-day race. The daily running distances of the four-day race were the following; 93 km, 120 km, 56 km and 59 km, respectively. Pre-race and post-race urine samples were collected on each day and analyzed by a monoclonal antibody technique. The urinary 8-OHdG content increased significantly on the first day and tended to decrease from the third day. By the fourth day 8-OHdG content was significantly less than measured on the first three days. The serum creatine kinase activity changed in a similar fashion, showing a large increase (P < 0.001) up to the third day when it decreased significantly from the peak value (P < 0.05). We conclude that extreme physical exercise causes oxidative DNA damage to well trained athletes. However, repeated extreme exercise-induced oxidative stress does not propagate on increase of urinary 8-OHdG, but rather causes an adaptation leading to normalization of oxidative DNA damage.

Energy cost of wheel running in house mice: implications for coadaptation of locomotion and energy budgets.

Laboratory house mice (Mus domesticus) that had experienced 10 generations of artificial selection for high levels of voluntary wheel running ran about 70% more total revolutions per day than did mice from random-bred control lines. The difference resulted primarily from increased average velocities rather than from increased time spent running. Within all eight lines (four selected, four control), females ran more than males. Average daily running distances ranged from 4.4 km in control males to 11.6 km in selected females. Whole-animal food consumption was statistically indistinguishable in the selected and control lines. However, mice from selected lines averaged approximately 10% smaller in body mass, and mass-adjusted food consumption was 4% higher in selected lines than in controls. The incremental cost of locomotion (grams food/revolution), computed as the partial regression slope of food consumption on revolutions run per day, did not differ between selected and control mice. On a 24-h basis, the total incremental cost of running (covering a distance) amounted to only 4.4% of food consumption in the control lines and 7.5% in the selected ones. However, the daily incremental cost of time active is higher (15.4% and 13.1% of total food consumption in selected and control lines, respectively). If wheel running in the selected lines continues to increase mainly by increases in velocity, then constraints related to energy acquisition are unlikely to be an important factor limiting further selective gain. More generally, our results suggest that, in small mammals, a substantial evolutionary increase in daily movement distances can be achieved by increasing running speed, without remarkable increases in total energy expenditure.

Tests of running performance do not predict subsequent spontaneous running in rats

Rats of similar mass and genetic stock have up to a 50-fold difference in spontaneous daily running distance. However, the reasons for this large variability in spontaneous running distance are not known. This study examined whether tests of running performance predict subsequent spontaneous running distance in rats housed in individual running wheel cages. Long-Evans rats ( n = 56) were randomly assigned to either a sedentary control group (C) or a group housed in specially designed wheel cages in which they were able to exercise spontaneously (ES). They then underwent a high-intensity running test (MAX), during which oxygen consumption was measured at a submaximal ( VO 2submax) and maximal workload ( VO 2max). The rats' submaximal running endurance (END) and maximal sprinting speed (SPRINT) were also tested on the treadmill. After 8 weeks the average spontaneous running distance of ES was 29.7 ± 3.7 km · wk −1 (mean ± SE), but ranged from 1.4 to 71.1 km · wk −1. Tests of running performance and oxygen consumption were repeated in both groups, followed by in situ measurements of muscle contractile properties and of citrate synthase activity in the skeletal muscle. None of the measurements of running performance or oxygen consumption during the initial tests conducted at the start of the experiment was related to subsequent average spontaneous running distance. After 8 weeks, the mean peak force generated by the electrically stimulated gastrocnemius/plantaris muscles was greater in ES than in C (746± 89 vs. 455 ± 28 mg, p < 0.005), but this difference was not related to spontaneous running distance. Conversely, citrate synthase activity of the soleus muscle after training was related to average spontaneous running distance ( r = 0.92, p < 0.0004). Average spontaneous running distance was also related to MAX ( r = 0.65, p < 0.002), END ( r = 0.59, p < 0.0009), and SPRINT ( r = 0.61, p < 0.0005) and was inversely related to running intensity ( r = −0.66, p < 0.002) after 8 weeks of training. It can be concluded from this study that 1) spontaneous running distance in rats cannot be predicted by pretraining tests of running performance. Hence, low levels of spontaneous running activity in some rats are not explained by skeletal muscular and cardiovascular factors thought to determine running capacity, and 2) posttraining tests of running performance were proportionally related to total spontaneous running distance and muscle oxidative enzyme changes but not to the in situ contractile properties of the muscles.

VOLUNTARY EXERCISE TRAINING ENHANCES GLUCOSE TRANSPORT IN SKELETAL MUSCLE STIMULATED BY INSULIN-LIKE GROWTH FACTOR-I 343

A single bout of exercise significantly increases the action of insulin-like growth factor-I (IGF-I) on glucose transport in rat skeletal muscle. However, it is currently unknown how chronic exercise training influences the stimulatory effect of IGF-I on muscle glucose transport. We have therefore measured IGF-I-stimulated glucose transport (by 2-deoxyglucose(2-DG) uptake) in the isolated epitrochlearis muscle of juvenile female Wistar rats after 1 or 2 weeks of voluntary wheel running. 2-DG uptake was determined in the absence or presence of sub-maximally (5 nM) and maximally (50 nM) effective doses of IGF-I. Average daily running distances were 5.8 ± 0.6 and 9.5 ± 1.1 km/day after 1 and 2 weeks, respectively. Exercise training did not affect 2-DG uptake in the absence of hormone. However, after 1 week of voluntary exercise training, rates of submaximal and maximal IGF-I-stimulated 2-DG uptake were 82% and 61% greater (p<0.05), respectively, than in age-matched sedentary control groups. An additional week of voluntary exercise training did not cause further enhancement of IGF-I action, as submaximal and maximal IGF-I-stimulated 2-DG uptake rates were 72% and 57% greater than control. GLUT-4 protein, the regulatable glucose transporter isoform in muscle, was significantly increased (+24% vs. sedentary control) only after 2 weeks of running. These results indicate that, in this model of volitional exercise training, rapid increases in IGF-I-stimulated muscle glucose transport are observed and are maximal after 1 week. In addition, these increases are not associated with the upregulation of GLUT-4 protein. The present findings support the concept that increased IGF-I action may contribute to enhanced glucoregulation after exercise training.

Running training alters fiber type composition in spinal muscles

The issue of whether exercise can induce changes in muscle fiber types has been long debated. Knowledge about the alterations in spinal muscle fiber types is scarce. In this study, the alterations initiated by long-distance running on spinal muscle fiber type distribution was studied. Ten young dogs were run on a treadmill for 55 weeks, 5 days a week, and ten dogs from the same litters served as controls. The daily running distance was gradually increased to 40 km and maintained at that level for the final 15 weeks. Histological sections were prepared from the cervical, thoracic, and lumbar multifidus muscles and the medial and lateral heads of triceps brachii and analyzed for the fiber type composition and cross-sectional area of fibers. In the lumbar multifidus, the numerical percentage of the muscle fibers with low oxidative capacity (type II) increased significantly in the running group. However, in the thoracic and cervical spine multifidus, the response to running resembled more of the significant shift from type II to type I fibers (with high oxidative capacity), which was also observed in the triceps brachii muscle. In these muscles, the quantitative image analysis of nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) reaction also demonstrated a shift towards a higher oxidative capacity within the type II fibers. The results show that training can induce changes in fiber type composition not only in limb muscles but also in the stabilizing spinal muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced prolylhydroxylase activity in the posterior annulus fibrosus of canine intervertebral discs following long-term running exercise

The effect of long-term excercise on the intervertebral disc collagen concentration (hydroxyproline), collagen-synthesizing enzymes (prolyl-4-hydroxylase, PH, and galactosyl-hydroxylysyl glucosyltransferase, GGT) and hydroxypyridinium crosslinks was studied in ten female beagle dogs. The dogs were run on a treadmill for 1 year starting at the age of 15 weeks. The daily running distance was gradually increased to 40km, which distance the dogs ran for the final 15 weeks. Ten untrained dogs from the same breeding colony served as controls. The nucleus pulposus and anterior and posterior halves of the annulus fibrosus of C2-3, T10-12, L4-5 disc segments were analysed. Crosslinks were measured from the anterior annulus fibrosus of the T10-11 disc. Hydroxyproline and hydroxypyridinium concentrations remained similar in both groups. PH and GGT were significantly elevated by running in the posterior annulus fibrosus of the thoracic and lumbar discs and in the lumbar nucleus pulposus. In the thoracic nucleus pulposus GGT was reduced significantly. The results suggest activated collagen metabolism in the posterior annulus fibrosus of the thoracic and lumbar discs as a result of locally increased strains on the spine.