Chronic social isolation compromises the activity of both glutathione peroxidase and catalase in hippocampus of male wistar rats

Abstract

Chronic neuroendocrine stress usually leads to the elevation of the stress hormones and increased metabolic rate, which is frequently accompanied by oxidative damage to the CNS. In the present study we hypothesized that chronic psychosocial isolation (CPSI) of male Wistar rats, characterized by decreased serum corticosterone (CORT), unaltered catecholamines (CTs), and low blood glucose (GLU), may also promote oxidative imbalance in the CNS, by targeting antioxidant defense system. To test it, we have examined the relation between these input signals and protein expression/activity of antioxidant enzymes (AOEs): superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GLR) in the hippocampus (HIPPO) of CPSI animals. We found that CPSI did not affect SODs or CAT, but decreased activity of GPx and compromised GLR, an enzyme highly dependent on blood GLU for its substrate precursor. Further, we have tested whether the CPSI experience altered AOEs response to a novelty stress, and found that it attenuated peroxide-metabolizing enzymes, CAT and GPx, and decreased GLR activity, even though blood GLU was restored. The altered ratios of hippocampal AOEs in CPSI animals, which were worsened under the combined stress conditions, may lead to the accumulation of peroxide products and oxidative imbalance. The mechanism by which CPSI generate oxidative imbalance in the HIPPO is most likely based on poor systemic energy conditions set by this stress. Such conditions may cause functional decline of CNS structures, such as HIPPO, and are likely to promote state linked to onset of many mood disorders.

Fig. 1

a Representative Western blots of CuZn-superoxide dismutases (CuZnSOD) protein expression in the cytosol (left panel) and Mn-superoxide dismutase (MnSOD) protein expression in the cytosol and in the mitochondria (right panel) in the hippocampus of stressed Wistar rats. b Relative quantification of CuZnSOD (left panel) and MnSOD (right panel) protein expression in the hippocampus obtained from 2 separate experiments each performed in triplicates. c Antioxidant enzyme activities of CuZnSOD (left panel) and MnSOD (right panel) in the hippocampus of control and stressed Wistar rats. Data are presented as mean ± SEM (as described under “Statistical analysis of data” section). * P < 0.05 stress vs. control, ^$P < 0.05 chronic vs. combined

Fig. 2

a Representative Western blots of catalase (CAT) protein expression in the cytosol (left panel) and in the peroxisomes (right panel) in the hippocampus of control and stressed Wistar rats. b Relative quantification of CAT protein expression in the cytosol (left panel) and in the peroxisomes (right panel) in the hippocampus obtained from 2 separate experiments each performed in triplicates. c Antioxidant enzyme activities of CAT in the cytosol (left panel) and in the peroxisomes (right panel) in the hippocampus of control and stressed Wistar rats. Data are presented as mean ± SEM (as described under “Statistical analysis of data” section). * P < 0.05 stress vs. control, ^%P < 0.05 acute vs. combined

Fig. 3

a Representative Western blots of glutathione peroxidase (GPx) protein expression in the cytosol (left panel) and glutathione reductase (GLR) protein expression in the cytosol (right panel) in the hippocampus of control and stressed Wistar rats. b Relative quantification of GPx protein expression (left panel) and GLR protein expression (right panel) in the cytosol in the hippocampus obtained from 2 separate experiments each performed in triplicates. c Antioxidant enzyme activities of GPx (left panel) and GLR (right panel) in the cytosol in the hippocampus of control and stressed Wistar rats. Data are presented as mean ± SEM (as described under “Statistical analysis of data” section). *P < 0.05 stress vs. control, ^%P < 0.05 acute vs. combined, ^$P < 0.05 chronic vs. combined