title: Acute immobilization stress following contextual fear conditioning reduces fear memory: timing is essential.
abstract: BACKGROUND
  Histone 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.
  
  
  METHODS
  Mice 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.
  
  
  RESULTS
  Freezing 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.
  
  
  CONCLUSIONS
  Acute 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.
authors.affiliation: Department of Biochemistry and Cell Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. akemi-uwaya@nms.ac.jp.
authors.forename: Akemi
authors.initials: A
authors.lastname: Uwaya
authors.affiliation: Department of Biochemistry and Cell Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. hyunjin@nms.ac.jp.
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, The Jikei University School of Medicine, 3-25-8, Nishi-Shimbashi, Minato-ku, Tokyo, 105-8641, Japan. park2014@jikei.ac.jp.
authors.forename: Jonghyuk
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Cell Biology and Neuroscience, Juntendo Medical School, 2-1, Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan. ho-lee@juntendo.ac.jp.
authors.forename: Hosung
authors.initials: H
authors.lastname: Lee
authors.affiliation: Graduate School of Health and Sport Science, Nippon Sport Science University, 7-1-1 Fukasawa, Setagaya-ku, Tokyo, 158-8508, Japan. noberusho@muto.opal.ne.jp.
authors.forename: Junko
authors.initials: J
authors.lastname: Muto
authors.affiliation: Kyoritsu Women's Junior College, 2-2-1 Hitotsubashi, Chiyoda-ku, Tokyo, 101-8437, Japan. sanakajima@kyoritsu-wu.ac.jp.
authors.forename: Sanae
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Department of Biochemistry and Cell Biology, Institute for Advanced Medical Sciences, Nippon Medical School, 1-396 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa, 211-8533, Japan. ohta@nms.ac.jp.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohta
authors.affiliation: Department of Health and Sport Science, Nippon Medical School, 1-7-1, Sakaiminami machi, Mushasino-shi, Tokyo, 180-0023, Japan. mikami@nms.ac.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Mikami
mesh_terms: D000107:Acetylation; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003214:Conditioning, Classical / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism*; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D005239:Fear / Q000502:physiology*; D015870:Gene Expression; D006624:Hippocampus / Q000502:physiology*; D006657:Histones / Q000378:metabolism; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012149:Restraint, Physical; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D006657:Histones; D003345:Corticosterone