Endurance capacity of mice selectively bred for high voluntary wheel running

Abstract

SUMMARYMice from four lines bred for high voluntary wheel activity run ~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, P<0.0001). Blood glucose following the treadmill test was low for all animals (~53 mg dl -1 ) and lactate was high (~6.5 mmol l -1 ), suggesting that exhaustion occurred. The HR lines had significantly higher endurance than the C lines (1-tailed P<0.05), whether or not body mass was used as a covariate in the analysis. The relationship between line means for wheel 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.Key words: artificial selection, endurance, exhaustion, experimental evolution, genetics, glucose, lactate, locomotor activity, wheel running. THE JOURNAL OF EXPERIMENTAL BIOLOGY THE JOURNAL OF EXPERIMENTAL BIOLOGY 2909Endurance capacity of high-activity mice Kelly et al., 2006), increased insulin-stimulated glucose uptake by isolated extensor digitorum longus muscle (Dumke et al., 2001), and more GLUT4 in the gastrocnemius after 5 days of wheel access (Gomes et al., 2009). In addition, blood haemoglobin concentration was a positive predictor of V O2max in the HR lines, but a negative predictor in the C lines (Rezende et al., 2006c). However, direct measurements of endurance-running ability have not yet been performed.The purpose of the present study was to test the hypothesis that HR mice have greater endurance than C mice in a graded-speed treadmill test (e.g. Lerman et al., 2002; Haubold et al., 2003). We also measured blood glucose and lactate concentrations at rest, during voluntary wheel running and at the end of the endurance test. We hypothesized that wheel running would increase blood lactate concentrations relative to those at rest, and that concentrations after the endurance test would be even higher. We also hypothesized that blood glucose concentrations would be decreased following the endurance trial compared with values at rest. In human beings, endurance-trained subjects e...

Are Voluntary Wheel Running and Open-Field Behavior Correlated in Mice? Different Answers from Comparative and Artificial Selection Approaches

“…Duman et al (2008) speculated that reduced locomotion in the open-field that was possibly related to immediate fatigue after running (see also Fuss et al 2010). This seems unlikely to us, however, as even our HR mice do not run voluntarily on wheels at speeds that exceed their maximal aerobic capacity Rezende et al 2005), nor do they show obvious signs of fatigue during or following wheel running (Meek et al 2009;personal observations). Alternatively, voluntary wheel running induces a significant elevation in circulating corticosterone in both HR and C mice (Girard and Garland 2002) and in C57BL/ 6N mice (Droste et al 2003).…”

Mice selectively bred for high voluntary wheel running have larger midbrains: support for the mosaic model of brain evolution

“…In fact, recent work in human 'ultra-endurance' athletes (Pearson, 2006) suggests that neurobiological attributes make a greater contribution to maximum performance ability than has previously been acknowledged (Kayser, 2003;Baden et al, 2005;Noakes, 2007;Rose and Parfitt, 2007;Noakes, 2008). In our laboratory, selection for high voluntary wheel running in outbred laboratory house mice has been ongoing for more than 60 generations, and has resulted in numerous physiological (Girard et al, 2007;Malisch et al, 2008;Gomes et al, 2009;Meek et al, 2009), behavioral (Rhodes et al, 2001Rhodes and Garland, 2003; Belke and Garland, 2007;Meek et al, 2010), and neurobiological (Rhodes et al, 2003a;Rhodes et al, 2003b) changes in four replicate high-runner (HR) lines of mice as compared with four non-selected control (C) lines. Moreover, a recent comparative study demonstrated a positive correlation between brain size and an index of exercise capacity, maximal oxygen consumption (Raichlen and Gordon, 2011), one of the traits that has increased in the HR lines (Rezende et al, 2006b;Kolb et al, 2010).…”

“…As compared with C mice, HR mice exhibit various anatomical (Garland and Freeman, 2005;Kelly et al, 2006) and physiological differences (Rezende et al, 2006a;Rezende et al, 2006b;Gomes et al, 2009;Meek et al, 2009) that appear to support their 2.5-to 3-fold greater daily wheelrunning distances. Although previous studies have revealed physiological (Dumke et al, 2001;Rezende et al, 2006a;Rezende et al, 2006b;Gomes et al, 2009;Meek et al, 2009;Kolb et al, 2010), morphological (Garland and Freeman, 2005;Kelly et al, 2006) and motivational (Rhodes et al, 2005; Belke and Garland, 2007) components underlying this HR phenotype, the present findings are the first evidence of neuroanatomical changes in the HR lines. [A previous study that quantified volume of the dentate gyrus of the hippocampus found no statistical difference between the HR and C lines (Rhodes et al, 2003a). ]…”

“…Mini-muscle individuals also differ from wild-type individuals in the size of some internal organs, including the heart, liver, spleen, lungs and kidneys [adjusting for variation in body size (e.g. Garland et al, 2002;Meek et al, 2009;Kolb et al, 2010; Downs et al, 2012)]. Therefore, it seemed reasonable to expect that minimuscle individuals might also differ in relative brain size.…”

Western diet increases wheel running in mice selectively bred for high voluntary wheel running

“…8,9 Various changes in locomotor performance, behavior and neurobiology (especially related to motivation for wheel running) have been observed in the HR lines. [10][11][12] For instance, treadmill endurance capacity is elevated in HR mice, 13 as is maximal oxygen consumption. 14 Despite the continued selection since generation 16, HR mice seem to be at a selection limit, the biological causes of which are not yet clear.…”