The effect of voluntary wheel running on the antioxidant status is dependent on sociability conditions

Abstract

Voluntary wheel running is widely used as a physical activity (PA) model in rodents, but most studies investigate the beneficial effects of this intervention in socially isolated mice. Social isolation stress (SIS) is associated with vulnerability to oxidative stress and reduced mitochondrial activity. Thus, the aim of this study was to investigate the effects of free access to a running wheel for 21 days on the various markers of the cellular redox/antioxidant status as well as mitochondrial function of mice subjected to SIS or maintained in groups of 3 in the homecage. SIS increased thiobarbituric acid reactive substance (TBARS) levels in the cerebral cortex, and PA intervention was not able to reverse such alteration. PA reduced TBARS levels in the liver of grouped mice and gastrocnemius of socially isolated mice. PA increased nonprotein thiol (NPSH) levels in the cerebral cortex of grouped mice. Furthermore, socially isolated mice presented lower glutathione peroxidase (GPx) activity in the cerebellum and gastrocnemius, and glutathione reductase (GR) activity in the cerebral cortex and liver. By contrast, SIS induced higher GPx activity in the cerebral cortex and heart. PA reduced GPx (cerebral cortex) and GR (cerebral cortex and liver) activities of socially isolated mice. SIS caused higher activity of mitochondrial complexes I and II in the cerebral cortex, and the PA paradigm was not able to alter this effect. Interestingly, the PA produced antidepressant-like effect at both SIS and control groups. In conclusion, the results showed the influence of SIS for the effects of PA on the antioxidant status, but not on the mitochondrial function and emotionality.

Keywords: Glutathione; Mitochondria; Oxidative stress; Physical activity; Social isolation stress; Voluntary wheel running.

Fig. 1

The effect of housing conditions (socially isolated or grouped animals) on the distance travelled and time spent during the voluntary physical activity. The effect of housing conditions on the area under the curve of the distance travelled (Panel A) or the time spent on the running wheel (Panel B) over 21 days. Data are presented as mean of the area under curve of six mice/group. ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice (Student's t-test).

Fig. 2

The effect of physical activity and/or chronic social isolation on the lipoperoxidation index. The effect of physical activity on the TBARS levels in the cerebral cortex (Panel A), cerebellum (Panel B), heart (Panel C), gastrocnemius (Panel D) and liver (Panel E) of the socially isolated or grouped mice. Data are presented as mean + SEM of six mice/group. ^⁎p < 0.05, ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice. ^#p < 0.05 as compared to sedentary grouped mice (two-way ANOVA followed by Newman-Keuls post-hoc test).

Fig. 3

The effect of physical activity and/or chronic social isolation on the non-protein thiols (NPSH) levels. The effect of physical activity on the NPSH levels in the cerebral cortex (Panel A), cerebellum (Panel B), heart (Panel C), gastrocnemius (Panel D) and liver (Panel E) of the socially isolated or grouped mice. Data are presented as mean + SEM of six mice/group. ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice (two-way ANOVA followed by Newman-Keuls post-hoc test).

Fig. 4

Physical activity and/or chronic social isolation induce alterations on the glutathione peroxidase (GPx) or glutathione reductase (GR) activities. The effect of physical activity on the GPx or GR activities in the cerebral cortex (Panels A and B, respectively), cerebellum (Panels C and D, respectively), heart (Panels E and F, respectively), gastrocnemius (Panels G and H, respectively), liver (Panels I and J, respectively) of the socially isolated or grouped mice. ^⁎p < 0.05, ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice. ^#p < 0.05 as compared to sedentary grouped mice (n = 6; two-way ANOVA followed by Newman-Keuls post-hoc test).

Fig. 5

The effect of physical activity and/or chronic social isolation on the complex I and II activities of mice. The effect of physical activity on the complex I or II activities in the cerebral cortex (Panels A and B, respectively) and gastrocnemius (Panels C and D, respectively), of the socially isolated or grouped mice. *p < 0.05 and ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice (n = 5–6; two-way ANOVA followed by Newman-Keuls post-hoc test).

Fig. 6

Voluntary wheel running induces antidepressant-like effect in the socially isolated and grouped animals. The effect of physical activity on the immobility time in the TST (Panel A) and the crossings and rearings in the open field test (Panels B and C, respectively) of the socially isolated or grouped mice. *p < 0.05 and ^⁎⁎p < 0.01 as compared to sedentary socially isolated mice (n = 9; two-way ANOVA followed by Newman-Keuls post-hoc test).

Fig. 7

Correlation between the oxidative stress-related parameters or behavior and the distance travelled or time spent on the running wheel of socially isolated mice. The correlation between distance travelled or time spent on the voluntary wheel running with: 1) TBARS levels in the cerebral cortex (Panels A and B), and cerebellum (Panels C and D); 2) GPx activity in the cerebellum (Panels E and F) and heart (Panels G and H); 3) GR activity in the gastrocnemius (Panels G and H); and the immobility time in the tail suspension test (Panels I and J).