title: 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. The role of epigenetic mechanisms that potentially contribute to these rescue or protective effects is also not known. The 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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Patki
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Naimesh
authors.initials: N
authors.lastname: Solanki
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Fatin
authors.initials: F
authors.lastname: Atrooz
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Ansari
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Farida
authors.initials: F
authors.lastname: Allam
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Brittany
authors.initials: B
authors.lastname: Jannise
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA.
authors.forename: Jaganmohan
authors.initials: J
authors.lastname: Maturi
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, University of Houston, TX, USA. Electronic address: ssalim@uh.edu.
authors.forename: Samina
authors.initials: S
authors.lastname: Salim
mesh_terms: D000107:Acetylation; D000818:Animals; D001008:Anxiety Disorders / Q000503:physiopathology* / Q000628:therapy; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D004291:Dominance-Subordination; D044127:Epigenesis, Genetic / Q000502:physiology; D006624:Hippocampus / Q000503:physiopathology*; D006657:Histones / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000503:physiopathology* / Q000628:therapy; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D009043:Motor Activity / Q000502:physiology*; D015213:Neuroimmunomodulation / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; C497394:Mecp2 protein, rat; D051783:Methyl-CpG-Binding Protein 2; D003345:Corticosterone
keywords: Anxiety; Cognition; Oxidative stress; Physical exercise; Social defeat
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