Novel mechanistic insights into treadmill exercise based rescue of social defeat-induced anxiety-like behavior and memory impairment in rats

Abstract

Social defeat (SD) induced stress causes physiological and behavioral deficits in rodents, including depression and anxiety-like behaviors, as well as memory impairment. Anxiolytic and mood elevating effects of physical exercise are also known. However, rescue effect of physical exercise in social defeat-induced anxiety, depression or memory impairment has not been addressed. Role of epigenetic mechanisms that potentially contribute to these rescue or protective effects are also not known. Present study investigated the effect of moderate treadmill exercise on anxiety-like behavior and memory function in rats subjected to SD using a modified version of the resident-intruder model for social stress (defeat). Changes in histone acetylation and histone-modifying enzymes were examined in hippocampus, amygdala and frontal cortex which are considered critical for anxiety, depression and cognition. Sprague Dawley rats were randomly assigned in four groups; control, exercised, social defeat, social defeat and exercise. At the end of the SD or control exposure lasting 30 min daily for 7 days, one group of SD rats was subjected to treadmill exercise for 2 weeks, whereas the other SD group was handled without exercise. Anxiety-like behavior tests and radial arm water maze test suggested that moderate treadmill exercise rescued social defeat induced anxiety-like behavior and memory impairment. Moreover, exercise normalized SD-induced increase in oxidative stress, most likely by adjusting antioxidant response. Our data suggests involvement of epigenetic mechanisms including histone acetylation of H3 and modulation of methyl-CpG-binding in the hippocampus that might contribute to the rescue effects of exercise in SD-induced behavioral deficits in rats.

Repeated forced swim stress prior to complete Freund’s adjuvant injection enhances mechanical hyperalgesia and attenuates the expression of pCREB and ΔFosB and the acetylation of histone H3 in the insular cortex of rat

“…The above-mentioned increase in the acetylation of histone H3 in the PFC is observed at 24 h after social defeat stress (Hinwood et al, 2011;Kenworthy et al, 2014). However consistent with our results, the long-lasting (about 2 weeks) change in the acetylation of histone H3 is also shown in the hippocampus after social defeat stress (Patki et al, 2014). It has been speculated that the histone acetylation in some brain areas including PFC correlates with susceptibility to social defeat stress (Kenworthy et al, 2014).…”

“…Some studies have demonstrated that social defeat stress increases the acetylation of histone H3 in the median prefrontal cortex (PFC) (Hinwood et al, 2011;Kenworthy et al, 2014). However the others have reported that there is no significant increase in acetylation of histone H3 in the frontal cortex after social defeat stress (Hollis et al, 2010;Patki et al, 2014). It might be one of the reasons of discrepancy between these studies is that the former study evaluated the change in smaller cortical area than the latter study.…”

Intermittent metabolic switching, neuroplasticity and brain health

“…Data from human and animal studies suggest that sedentary, overindulgent lifestyles increase the risk of anxiety disorders and depression 155 and that IMS effected by exercise or IF can improve mood and ameliorate anxiety and depression 156–159 . The ability of exercise to ameliorate symptoms of depression and anxiety is well known, and the underlying mechanisms have been elucidated, with upregulation of BDNF expression in neuronal circuits that regulate mood playing a role 160–162 .…”

Epigenetic programming of the neuroendocrine stress response by adult life stress

“…Physical exercise has been shown to improve cognitive responses to psychosocial stress and rescue rats from social defeat-induced anxiety-like behaviour and memory impairment ). This beneficial effect might potentially be mediated by epigenetic mechanisms, including exercise-induced H3 acetylation and modulation of methylation in the hippocampus (Patki et al 2014).…”