title: Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.
abstract: Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation.
authors.affiliation: Behavioral Neurophysiology Laboratory, Universidad Nacional de Colombia, Bogotá, Colombia; Physiological Sciences Department, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Viviana
authors.initials: V
authors.lastname: Vargas-López
authors.affiliation: Behavioral Neurophysiology Laboratory, Universidad Nacional de Colombia, Bogotá, Colombia; Psychology Department, School of Human Sciences, Universidad Nacional de Colombia, Bogotá, Colombia.
authors.forename: Marisol R
authors.initials: MR
authors.lastname: Lamprea
authors.affiliation: Behavioral Neurophysiology Laboratory, Universidad Nacional de Colombia, Bogotá, Colombia; Physiological Sciences Department, School of Medicine, Universidad Nacional de Colombia, Bogotá, Colombia. Electronic address: famunerag@unal.edu.co.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Múnera
mesh_terms: D000107:Acetylation; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003345:Corticosterone / Q000378:metabolism*; D044127:Epigenesis, Genetic / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism*; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013315:Stress, Psychological / Q000150:complications / Q000378:metabolism / Q000517:prevention & control
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D003345:Corticosterone
keywords: Acute stress; Corticosterone; Epigenetics; Histone deacetylation; Spatial memory; Stress induced-memory impairment; Trichostatin A