Brown M, Booth FW. Phenotypic and molecular differences between rats selectively bred to voluntarily run high vs. low nightly distances. Am J Physiol Regul Integr Comp Physiol 304: R1024-R1035, 2013. First published April 3, 2013 doi:10.1152/ajpregu.00581.2012.-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 Ͻ 0.001), spent less time running (P Ͻ 0.001), and ran slower (P Ͻ 0.001) than their G8 male and female HVR counterparts, respectively. HVR and LVR lines consumed similar amounts of standard chow with or without wheels. No inherent difference existed in PGC-1␣ 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 ϭ 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 Ͼ1.5-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. selective breeding; exercise; genes; nucleus accumbens; RNA-seq APPROXIMATELY 97% OF US adults and 92% of adolescents are not meeting US daily physical activity guidelines for 30 and 60 min, respectively (44). The clinical significance of lack of sufficient daily physical activity is an increased prevalence of 35 chronic unhealthy conditions and premature death (5). Motivation, fitness, and genes are all associated with physical activity levels (4). Twin and family studies have shown that genetic factors contribute to variation in reported daily physical activity levels, with identical cotwins showing smaller intraindividual variation than nontwins (see Ref. 4 for references).Animal studies also suggest that brain mechanisms affect the quantity of daily voluntary running (14,21,22,36,38).One approach to obtain genetic information on genes and physical activity has been to employ a selective breeding model of physical activity in rodents. According to Rhodes et al. (35), selective breeding is a "powerful alternative" compared with knockout models in studying genotype-phenotype interactions, given that multiple genes contribute to complex phenotypes. Swallow et al. (42) have phenotyped their 10th generation of mice selected for the highest revolutions per day of wheel running, these being ...

Key pointsr Selective breeding experiments with laboratory rodents have demonstrated the heritability of voluntary exercise.r We performed RNA sequencing and bioinformatics analyses of the reward and pleasure hub in the brain -the nucleus accumbens -in rats selectively bred for low voluntary running (LVR) versus high voluntary running (HVR).r The discovery of unique genes and 'cell cycle'-related gene pathways between lines guided our hypothesis that neuron maturation may be lower in LVR rats.r Testing of this hypothesis revealed that the LVR line inherently possessed fewer mature medium spiny neurons and fewer immature neurons than their HVR counterparts. However, minimal running in LVR rats appeared to rescue and/or reverse these effects.r Neuron maturation in the nucleus accumbens is related to low running voluntary behaviour in our model; this allows researchers to understand the potential neural mechanisms that underlie the motivations for low physical activity behaviour.Abstract 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 (LVR non-run and HVR non-run ), as well as in rats after 6 days of voluntary wheel running (LVR run and HVR run ). 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 LVR non-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P < 0.001) and fewer immature (Dcx-positive) neurons (P < 0.001) than their G9-10 HVR counterparts. However, voluntary 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.

Reduced balance function has been observed during balance challenging conditions in the chronic obstructive pulmonary disease (COPD) population and is associated with an increased risk of falls. This study aimed to examine postural balance during quiet standing with eyes open and functional balance in a heterogeneous group of COPD and non-COPD (control) subjects, and to identify risk factors underlying balance impairment using a large panel of methods. In COPD and control subjects, who were mostly overweight and sedentary, postural and functional balance were assessed using center-of-pressure displacement in anterior-posterior (AP) and medio-lateral (ML) directions, and the Berg Balance Scale (BBS), respectively. COPD showed 23% greater AP sway velocity (p = 0.049). The presence of oxygen therapy, fat mass, reduced neurocognitive function, and the presence of (pre)diabetes explained 71% of the variation in postural balance in COPD. Transcutaneous oxygen saturation, a history of exacerbation, and gait speed explained 83% of the variation in functional balance in COPD. Neurocognitive dysfunction was the main risk factor for postural balance impairment in the control group. This suggests that specific phenotypes of COPD patients can be identified based on their type of balance impairment.