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

Hindawi Publishing Corporation The Scientific World Journal Volume 2013, Article ID 237260, 7 pages http://dx.doi.org/10.1155/2013/237260 Research Article Substrains of Inbred Mice Differ in Their Physical Activity as a Behavior Dario Coletti,1,2,3 Emanuele Berardi,4 Paola Aulino,1,2,3 Eleonora Rossi,2,3 Viviana Moresi,2,3 Zhenlin Li,1 and Sergio Adamo2,3 1 UR4 Aging, Stress, Inflammation, University Pierre et Marie Curie Paris 6, 7 Quai Saint Bernard, 75005 Paris, France Department of Anatomical, Histological, Forensic & Orthopaedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome, Via Scarpa 16, 00161 Rome, Italy 3 Interuniversity Institute of Myology, 00161 Rome, Italy 4 Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Katholieke Universiteit Leuven, 3000 Leuven, Belgium 2 Correspondence should be addressed to Dario Coletti; Received 30 December 2012; Accepted 4 February 2013 Academic Editors: L. Guimarães-Ferreira, H. Nicastro, J. Wilson, and N. E. Zanchi Copyright © 2013 Dario Coletti et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Recent studies strengthen the belief that physical activity as a behavior has a genetic basis. Screening wheel-running behavior in inbred mouse strains highlighted differences among strains, showing that even very limited genetic differences deeply affect mouse behavior. We extended this observation to substrains of the same inbred mouse strain, that is, BALB/c mice. We found that only a minority of the population of one of these substrains, the BALB/c J, performs spontaneous physical activity. In addition, the runners of this substrain cover a significantly smaller distance than the average runners of two other substrains, namely, the BALB/c ByJ and the BALB/c AnNCrl. The latter shows a striking level of voluntary activity, with the average distance run/day reaching up to about 12 kilometers. These runners are not outstanders, but they represent the majority of the population, with important scientific and economic fallouts to be taken into account during experimental planning. Spontaneous activity persists in pathological conditions, such as cancer-associated cachexia. This important amount of physical activity results in a minor muscle adaptation to endurance exercise over a three-week period; indeed, only a nonsignificant increase in NADH transferase+ fibers occurs in this time frame. 1. Introduction Exercise adaptations result from a coordinated response of multiple organ systems, including cardiovascular, pulmonary, endocrine-metabolic, immunologic, and skeletal muscle, recently reviewed by Boveris and Navarro [1], by Freidenreich and Volek [2], and by Perrino et al. [3]. Exercise training has been suggested as a promising countermeasure to prevent several disease states and as a rehabilitation tool aimed to restore both muscle strength and endurance, depending on the type of exercise [4]. Regular resistance exercise combined with adequate protein intake to maintain muscle mass is proposed to counteract sarcopenic obesity in an aging global population, a major public health challenge [5]. For all the above, rodent models of caloric intake and exercise are widely used [6] and novel molecular mechanisms underlying the effects of physical activity have been recently brought to light [7, 8]. Nonetheless, the anatomy and physiology of rodents differ significantly from those of humans. While it appears clear that Homo sapiens has evolved to support the svelte phenotype of an endurance runner [9], a better understanding of similarities and differences between human and animal models is becoming of paramount importance for translating discoveries in preclinical models to clinical settings. The two main types of contractile activity that are classified as low muscular tension development over an extended duration, or high-tension generation of limited duration, are characteristic of endurance and resistance exercise, respectively. The aforementioned adaptive responses at the whole body and cellular and molecular levels depend on the mode of 2 exercise performed [10]. For instance, increased strength [11– 13], power [14], muscle cross-sectional area [15–17], RNA, and protein content [18] typically occur following resistance exercise training. Aerobic, endurance exercise training has been shown to enhance exercise capacity [19], augment maximal oxygen consumption [20], increase oxidative enzymes [21], and elevate mitochondrial content [22]. Several protocols of exercise training were developed for rodent models to mimic either resistance or endurance exercise. For instance, to climb a vertical ladder as a mode of progressive resistance exercise has been used for rats [23]. Recently, a very interesting equipment and system of resistance exercise, based on squat-type exercise for rodents, with control of training variables, has been validated [24]. The latter is based on a conditioning system composed of sound, light, and feeding devices, thus being not necessary to impose fasting or electric shock for the animal to perform the task proposed. Endurance exercise is based on more standardized protocols, basically running. The intensity-controlled treadmill exercise represents a well-characterized model of endurance exercise [25]. Slope and velocity of treadmill can be regulated and the animals are hosted in an enclosed chamber with a shock grid for motivating mice to run. One of its major advantages is the possibility of increasing timewise exercise intensity, thus allowing the researcher to submit rodents to specific training programs. One of the drawbacks of treadmill is the fact that it may induce stress in the mice due to environmental, nonphysiological conditions. On the contrary, spontaneous exercise is often the favored type of exercise for experimental purposes since it is physiologic: it is performed at will, mostly during the nighttime; it mimics natural behavior, such as intermittent locomotion, typical of wildtype rodents; finally, it has been shown that such a voluntary activity is repeatable and stable within individual mice [26]. Hosting the mice in wheel-equipped cages, in which they exercise at will, classically induces such a spontaneous physical activity. A drawback of this approach is a certain degree of inter and intrapopulation variability, which makes absolutely necessary to individually monitor running activity by tachometers. Small genetic differences may have a great influence on behavioral phenotypes [27]. Thus, the genetic background of different substrains should be carefully chosen, equated, and considered in the interpretation of mutant behavioral phenotypes. To this purpose, Knab et al. assessed the repeatability of a commonly used maximal exercise endurance treadm (...truncated)