A temporal analysis of the relationships between social stress, humoral immune response and glutathione-related antioxidant defenses.

The exposure to different kinds of stress impacts on the reactive oxygen species production with potential risk to the integrity of the tissues. Psychological or biological stress is responsible for a significant increase in the oxidative stress markers and also for activation of the antioxidant defense system. In this study, we analyzed the relationships between social stress, humoral immune response and glutathione-related antioxidant defenses. Groups of male Swiss mice were subjected to different lengths of social stress exposure (social confrontation) which varied from 1 up to 13 days. As a biological stressor, 10(9) sheep red blood cells (SRBC)/mL were injected by intraperitoneal route. As controls, animals not subjected to social stress and/or injected with vehicle solution were used. The serum samples and the cerebral cortex were collected at 4 h, 3, 5, 7, 9, 11, and 13 days after the end of social confrontation. The results indicated that the antioxidant enzymes activities were affected by psychological as well as by biological stressor. These alterations were dependent on the timing of stress exposure which resulted in a positive or in a negative correlation between the antibody titres to SRBC and antioxidant enzymes. We also discuss the possible role of SRBC injection in the modulation of the effects of psychosocial stress on antioxidant metabolism.

Alterations in glutathione levels of brain structures caused by acute restraint stress and by nitric oxide synthase inhibition but not by intraspecific agonistic interaction.

Glutathione is the major non-protein thiol to which many different roles in the central nervous system (CNS) are attributed. To further investigate the glutathione response in the CNS, we tested the effect of three stress models on glutathione levels in the brain. We tested the effect of two models of repeated intraspecific agonistic interaction in mice. No influence was observed over the glutathione levels in the mice cerebral cortex, cerebellum, liver, and blood. Acute restraint stress in rats was found to induce an increase in glutathione levels in the cerebellum after 2 and 4 h of immobilization, an effect not observed in the cerebral cortex, striatum, and hippocampus. To investigate the interference of an inhibitor of nitric oxide synthase (NOS), N(omega)Nitro-L-arginine-methyl-ester (L-NAME, 50 mg/kg) was applied i.p. at the beginning of restraint stress. L-NAME alone did not lead to a change in glutathione levels although, in combination with restraint stress, it induced an increase in such levels. This effect was observed in all four structures studied, i.e. cortex, hippocampus, striatum, and cerebellum. The values returned to basal levels after 6h of immobilization. In conclusion, the pattern of dominance, after repeated intraspecific agonistic interaction, was ineffective in producing alterations in brain glutathione, whereas acute restraint stress led to an increase in glutathione levels within a window of 2-4 h, and the inhibition of NOS increased glutathione levels in all studied rat brain structures, suggesting a specificity interference of acute restraint stress with the glutathione system.

Long-term consequences of social stress on corticosterone and IL-1beta levels in endotoxin-challenged rats.

Social stress has strong and long-lasting effects on autonomic nervous, neuroendocrine and behavioural functioning. The functionality of the immune system is profoundly influenced by autonomic nervous and neuroendocrine activities. Changes in sympathetic-adrenal and hypothalamic-pituitary-adrenocortical (HPA) axis activities as observed during and after social defeat, therefore, probably represent an important factor in the modulation of the immune response. In the present study, the impact of social defeat stress on the responsiveness of the immune system was studied by the presentation of a systemic inflammatory challenge through the injection of the bacterial endotoxin lipopolysaccharide (LPS). Male Wistar rats were subjected twice to social defeat 7 days apart. One week after the second defeat, they were injected with LPS in a low (150 microg/kg; DLPS). Another group of defeated rats was injected with saline. Control, nondefeated rats also received the immune challenges. Previously defeated rats responded to the high dose of LPS with a deficient corticosterone (CORT) response resulting in an aggravated interleukin-1beta (IL-1beta) response 4 h after LPS injection. Furthermore, the experiments indicated that mortality rates after LPS administration were high in previously defeated rats, whereas mortality was absent in nondefeated rats. The results indicate that social stress has long-lasting effects on the functioning of the immune system and that it can seriously compromise the effectiveness of the adrenocortical response in containing some immunological defense mechanisms.