Mechanisms underlying spacing effect of memory

• Project/Area Number: 25560382
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology
• Principal Investigator: ENDO Shogo 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究部長 (60192514)
• Co-Investigator(Renkei-kenkyūsha): YANAI Shuichi 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (60469070) ; ARASAKI Tomoko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 技術員 (90645855)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 記憶 / 学習 / リハビリテーション / 小脳 / 一酸化窒素 / 活性酸素種 / 眼球運動 / 8-ニトロ-cGMP / グアニル化 / 休憩 / 分散学習

Outline of Final Research Achievements

Motor learning is a basis for the physical rehabilitation. The spaced training efficiently forms long-term memory compared to the massed training. The existence of spacing effect in memory mechanisms indicates the importance of the inter-trial-interval (the rest). The mechanisms underlying long-term during the inter-trial-interval, however, is largely unknown. In this research, first, we established the long-term adaptation of optokinetic response as a simple model of motor memory. Then, we demonstrated the 30 and 60 min inter -trial-interval works efficiently for the formation of the long-term adaptation. In addition, we analyzed reactive oxygen species-nitric oxide pathway as a potential system underlying spacing effect and identified components of the pathway in the cerebellum, the center of motor learning.

Research Products

• [Journal Article] Cilostazol improves hippocampus-dependent long-term memory in mice (2014)
  • Author(s): Shuichi Yanai, Yuki Semba, Hideki Ito, & Shogo Endo
  • Journal Title: Psychopharmacology Volume: - Issue: 13 Pages: 2681-2693
  • DOI: 10.1007/s00213-014-3442-4
  • Peer Reviewed
• [Journal Article] Targeted deletion of ERK2 in cardiomyocytes attenuates hypertrophic response but provokes pathological stress induced cardiac dysfunction. (2014)
  • Author(s): Ulm S, Liu W, Zi M, Tsui H, Chowdhury SK, Endo S, Satoh Y, Prehar S, Wang R, Cartwright EJ, Wang X.
  • Journal Title: J Mol Cell Cardiol Volume: 72C Pages: 104-116
  • DOI: 10.1016/j.yjmcc.2014.03.002
  • Peer Reviewed
• [Journal Article] Sialyltransferase ST3Gal IV deletion protects against temporal lobe epilepsy. (2014)
  • Author(s): P. Srimontri, S. Endo, T. Sakamoto, Y. Nakayama, A. Kurosaka, S. Itohara, Y. Hirabayashi, K Kato.
  • Journal Title: J Neurochem. Volume: 131 Issue: 5 Pages: 675-687
  • DOI: 10.1111/jnc.12838
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] The effect of diazepam on mouse PTSD-like behaviors induced by the 2011 Tohoku earthquake. (2014)
  • Author(s): S. Yanai, Y. Semba, and S. Endo.
  • Journal Title: Behav Sci Res Volume: 53 Pages: 27-36
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Deficits in memory-guided limb movements impair obstacle avoidance locomotion in Alzheimer’s disease mouse model (2014)
  • Author(s): Setogawa S, Yamaura H, Arasaki T, Endo S, Yanagihara D
  • Journal Title: Scientific Reports Volume: 4:7200 Issue: 1 Pages: 1-10
  • DOI: 10.1038/srep07220
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Exome sequencing of senescence-accelerated mice (SAM) reveals deleterious mutations in degenerative disease-causing genes. (2013)
  • Author(s): Tanisawa K., Mikami E., Fuku N., Honda Y., Honda S., Ohsawa I., Ito M., Endo S., Ihara K., Ohno K., Kishimoto Y., Ishigami A., Maruyama N., Sawabe M., Iseki H., Okazaki Y., Hasegawa-Ishii S., Takei S., Shimada A., Hosokawa M., Mori M., Higuchi K., Takeda T., Higuchi M., Tanaka M.
  • Journal Title: BMC Genomics. Volume: 14(1): Issue: 1 Pages: 248-248
  • DOI: 10.1186/1471-2164-14-248
  • Peer Reviewed / Open Access
• [Journal Article] Hepatic extracellular signal-regulated kinase 2 suppresses endoplasmic reticulum stress and protects from oxidative stress and endothelial dysfunction (2013)
  • Author(s): Kujiraoka T, Satoh Y, Ayaori M, Shiraishi Y, Arai-Nakaya Y, Hakuno D, Yada H, Kuwada N, Endo S, Isoda K, Adachi T.
  • Journal Title: J Am Heart Assoc Volume: 2 Issue: 4
  • DOI: 10.1161/jaha.113.000361
  • Peer Reviewed
• [Journal Article] Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice. (2013)
  • Author(s): Sakamoto, T., and Endo, S.
  • Journal Title: PLoS ONE Volume: 8 Issue: 3 Pages: e59880-e59880
  • DOI: 10.1371/journal.pone.0059880
  • Peer Reviewed
• [Journal Article] 神経可塑性・記憶におけるMEK1/2-ERK1/2の役割、 (2013)
  • Author(s): 遠藤昌吾
  • Journal Title: Clinical Neuroscience Volume: 31 Pages: 688-691
• [Journal Article] MAPKカスケード (2013)
  • Author(s): 佐藤泰司、遠藤昌吾
  • Journal Title: Clinical Neuroscience Volume: 31 Pages: 649-649
• [Presentation] Maintenance of memory functions by chronic administration of cilostazol, a phosphodiesterase 3 inhibitor, in aged mice models. (2014)
  • Author(s): Shuichi Yanai, Kai Kojima, Tomoko Arasaki & Shogo Endo
  • Organizer: Annual meeting of Society for Neuroscience
  • Place of Presentation: Washignton D.C., USA
  • Year and Date: 2014-11-15 – 2014-11-19
• [Presentation] Cilostazol,a phosphodiesterase 3 inhibitor, improves memories in senescence accelerated mice. (2014)
  • Author(s): S. Yanai, T. Arasaki, and S. Endo.
  • Organizer: Annual Meeting of the Japan Neuroscience Society
  • Place of Presentation: Yokohama, Japan
  • Year and Date: 2014-09-11 – 2014-09-13
• [Presentation] Phosphodiesterase 3 inhibitor cilostazol improves conditioned fear in SAM-P8 mice. (2014)
  • Author(s): S. Yanai, K Kojima, T. Arasaki, and S. Endo.
  • Organizer: Annual meeting of Japan Society for Biomedical Gerontology
  • Place of Presentation: Obu, Aichi, Japan
  • Year and Date: 2014-07-26 – 2014-07-27
• [Presentation] 記憶改善薬のスクリーニングとSAM (2014)
  • Author(s): 遠藤昌吾
  • Organizer: SAM研究協議会研究発表会
  • Place of Presentation: 東京
  • Year and Date: 2014-07-05
  • Invited
• [Presentation] Allodynia is reduced in mice deficient for ERK2. (2014)
  • Author(s): Y. Satoh, Y. Otsubo, G. Pagès, J. Pouysségur, S. Endo, T. Kazama.
  • Organizer: 2014
  • Place of Presentation: Taipei, Taiwan
• [Presentation] Abnormal neuropathic pain in mice deficient for ERK2 in the central nervous system. (2013)
  • Author(s): Otsubo Y., Satoh Y., Kodama M., Araki Y., Satomoto M., Sakamoto E., Pages G., Pouyssegur J., Endo S., Kazama T.
  • Organizer: 8th “Pain in Europe” Congress
  • Place of Presentation: Florence, Italy
• [Presentation] Deletion of hepatic ERK2 decreased the SERCA2 expressions, which can account for vascular oxidative stress and endothelial dysfunction in metabolic stress. (2013)
  • Author(s): T. Adachi, T. Nanba, Y. Satoh, M. Ayaori, Y. Shiraishi, Y.Arai-Nakaya, D. Hakuno, H. Yada, K. Isoda, S. Endo, T. Kujiraoka
  • Organizer: 11th International symposium on mechanisms on vasodilation,
  • Place of Presentation: Zurich, Switzerland
• [Presentation] Annormal pain in mice deficient for ERK2 in the central nervous system. (2013)
  • Author(s): Y. Otsubo-iwama, Y. Satoh, S.Endo, G. Pages, J. Pouysegur, T. Yamamoto, Y. Takahashi, T. Kazama
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Deficits in working memory related to obstacle avoidance during locomotion in Alzheimer’s disease mutant mice. (2013)
  • Author(s): S. Setogawa, H. Yamaura, S. Endo, D. Yanagihara.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Deep cerebellar nuclei play an important role in two-tone discrimination on delay eyeblink conditioning in C57BL/6 mice. (2013)
  • Author(s): T. Sakamoto, S. Endo.
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
• [Presentation] Distribution of 8-nitro-cGMP and S-guanylated proteins in cerebellum. (2013)
  • Author(s): S. Endo, M. Nakamura,T. Arasaki,T. Akaike
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Kyoto, Japan
• [Presentation] Cilostazol, a PDE3 inhibitor, improves learning and memory in mice. (2013)
  • Author(s): S. Yanai, Y. Semba, S. Endo.
  • Organizer: Japan Neuroscience Society
  • Place of Presentation: Kyoto, Japan
• [Book] Brain Aging and Therapeutic Interventions (Thakur and Rattan Ed.) (2013)
  • Author(s): Shogo Endo
  • Total Pages: 296
  • Publisher: Springer
• [Remarks] 記憶神経科学、東京都老人研
  • URL: http://www2.tmig.or.jp/Mn_B/Japanese/index.html
• [Remarks] 記憶神経科学、東京都老人研
  • URL: http://www2.tmig.or.jp/Mn_B/Japanese/