Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress

Abstract

In the present study, we have examined the behavioral and biochemical effect of induction of psychological stress using a modified version of the resident-intruder model for social stress (social defeat). At the end of the social defeat protocol, body weights, food and water intake were recorded, depression and anxiety-like behaviors as well as learning-memory function was examined. Biochemical analysis including oxidative stress measurement, inflammatory markers and other molecular parameters, critical to behavioral effects were examined. We observed a significant decrease in the body weight in the socially defeated rats as compared to the controls. Furthermore, social defeat increased anxiety-like behavior and caused memory impairment in rats (P<0.05). Socially defeated rats made significantly more errors in long term memory tests (P<0.05) as compared to control rats. Furthermore, brain extracellular signal-regulated kinase-1/2 (ERK1/2), and an inflammatory marker, interleukin (IL)-6 were activated (P<0.05), while the protein levels of glyoxalase (GLO)-1, glutathione reductase (GSR)-1, calcium/calmodulin-dependent protein kinase type (CAMK)-IV, cAMP-response-element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) were significantly less (P<0.05) in the hippocampus, but not in the prefrontal cortex and amygdala of socially defeated rats, when compared to control rats. We suggest that social defeat stress alters ERK1/2, IL-6, GLO1, GSR1, CAMKIV, CREB, and BDNF levels in specific brain areas, leading to oxidative stress-induced anxiety-depression-like behaviors and as well as memory impairment in rats.

Simultaneous Changes in Sleep, qEEG, Physiology, Behaviour and Neurochemistry in Rats Exposed to Repeated Social Defeat Stress

“…In the subordinate animals, alterations in brain activity were associated with a marked decrease in EEG power over the frequency range of 0.5-30 Hz and a sharp transient increase in slow-wave activity. This major novel finding in the defeated subordinate animals (a remarkable flattening of EEG power between 0 and 30 Hz) was accompanied with a marked increase in body temperature and a decrease in locomotor activity, a dissociation that in view of the EEG changes may reflect increased brain activity and higher oxidative metabolism and inflammatory mediators [42,43]. However, such EEG alterations disappeared at the end of the stress conditions.…”

Effect of Anti-stress Activity of Fluoxetine on Restrained Stress Induced Male Albino Rats in Hematological Parameters and Whole Brain Histopathology

“…Our findings are in agreement with other studies showing that the production of ROS by immune cells might be influenced by psychological stress. However, the available results in reference to the influence of psychological stress on the production of ROS are contradictory, 16,17 while others have shown a decreased ROS production. 18,19 This discrepancy may have been the result of a number of research design problems, including age, sex, intensity and type of stressor, plasma concentration of catecholamine and lack of adequate non-stressed controls, which are very important since a circadian rhythm in the generation of these compounds has been described.…”

Oxidative Stress and the Central Nervous System

“…For example, hippocampus, amygdala, and cerebellar granule cells have been reported as the most susceptible to oxidative stress in some studies (Wang and Michaelis, 2010), and consequently are purported to be the first to undergo functional decline. Our own preclinical work has suggested that behavioral and cognitive deficits are attributed to three brain regions: hippocampus, amygdala, and prefrontal cortex (PFC) (Masood et al, 2008;Salim et al, 2010aSalim et al, ,b, 2011aPatki et al, 2013a;2013b;Solanki et al, 2015). Hippocampus seems to be at the hot seat, and it appears that this brain region undergoes major biochemical changes that ultimately determine neuronal connections and function.…”