Abstract
BackgroundHistone acetylation is regulated in response to stress and plays an important role in learning and memory. Chronic stress is known to deteriorate cognition, whereas acute stress facilitates memory formation. However, whether acute stress facilitates memory formation when it is applied after fear stimulation is not yet known. Therefore, this study aimed to investigate the effect of acute stress applied after fear training on memory formation, mRNA expression of brain-derived neurotrophic factor (BDNF), epigenetic regulation of BDNF expression, and corticosterone level in mice in vivo.MethodsMice were subjected to acute immobilization stress for 30 min at 60 or 90 min after contextual fear conditioning training, and acetylation of histone 3 at lysine 14 (H3K14) and level of corticosterone were measured using western blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. A freezing behavior test was performed 24 h after training, and mRNA expression of BDNF was measured using real-time polymerase chain reactions. Different groups of mice were used for each test.ResultsFreezing behavior significantly decreased with the down-regulation of BDNF mRNA expression caused by acute immobilization stress at 60 min after fear conditioning training owing to the reduction of H3K14 acetylation. However, BDNF mRNA expression and H3K14 acetylation were not reduced in animals subjected to immobilization stress at 90 min after the training. Further, the corticosterone level was significantly high in mice subjected to immobilization stress at 60 min after the training.ConclusionAcute immobilization stress for 30 min at 60 min after fear conditioning training impaired memory formation and reduced BDNF mRNA expression and H3K14 acetylation in the hippocampus of mice owing to the high level of corticosterone.Electronic supplementary materialThe online version of this article (doi:10.1186/s12993-016-0092-1) contains supplementary material, which is available to authorized users.
Highlights
Histone acetylation is regulated in response to stress and plays an important role in learning and memory
Time course of histone acetylation in the hippocampus (Experiment 1) Memory formation induced by contextual fear conditioning training requires histone acetylation that occurs during a short period following such training [3]
Acetylation of H4 at lysine 5 (H4K5) did not change at any time point (Fig. 1c, Additional file 2: Table S2). These findings indicate that acetylation of histone 3 at lysine 14 (H3K14), but not histone 4 at lysine 5 (H4K5), is involved in memory formation, and that the critical timing for histone acetylation is from 60 to 90 min after the training
Summary
Histone acetylation is regulated in response to stress and plays an important role in learning and memory. This study aimed to investigate the effect of acute stress applied after fear training on memory formation, mRNA expression of brain-derived neurotrophic factor (BDNF), epigenetic regulation of BDNF expression, and corticosterone level in mice in vivo. Adrenal glands release corticosterone in response to stress, and this hormone plays an important role in memory formation [1, 2]. It triggers the transcription of brainderived neurotrophic factor (BDNF) via the activation of the N-methyl-d-aspartic acid (NMDA) receptor. Contextual fear training increases histone acetylation [3] and BDNF promoter binding to acetylated histone [12], followed by the consolidation of memory [12]; further, inhibition of histone deacetylation facilitates memory formation [9], indicating that the regulation of BDNF via histone acetylation plays an important role in memory formation [3, 13]
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