Ultrasound stress compromises the correlates of emotional-like states and brain AMPAR expression in mice: effects of antioxidant and anti-inflammatory herbal treatment

The modern lifestyle is associated with exposure to “psychological” or “emotional” stress. A growing portion of the population is exposed to emotional stress that results in a high incidence of anxiety disorders, a serious social problem. With this rise, there is a need for understanding the neurobiological causes of stress-induced anxiety and to offer safe remedies for this condition. Side effects of existing pharmaceuticals necessitate the search for alternatives. Having fewer adverse effects than classic remedies, natural extract-based therapies can be a promising solution. Here, we applied a model of emotional stress in BALB/c mice using ultrasound exposure to evoke the signs of anxiety-like behavior. We examined the behavioral and molecular impact of ultrasound and administration of herbal antioxidant/anti-inflammatory treatment (HAT) on AMPA receptor expression, markers of plasticity, inflammation and oxidative stress. A 3-week ultrasound exposure increased scores of anxiety-like behaviors in the standard tests and altered hippocampal expression as well as internalization of AMPA receptor subunits GluA1-A3. Concomitant treatment with HAT has prevented increases of anxiety-like behaviors and other behavioral changes, normalized hippocampal malondialdehyde content, GSK3β and pro-inflammatory cytokines Il-1β and Il-6, and the number of Ki67-positive cells. Levels of malondialdehyde, a common measure of oxidative stress, significantly correlated with the investigated end-points in stressed, but not in non-stressed animals. Our results emphasize the role of oxidative stress in neurobiological abnormalities associated with experimentally induced condition mimicking emotional stress in rodents and highlight the potential therapeutic use of anti-oxidants like herbal compositions for management of stress-related emotional disturbances within the community.