Synaptic maturation and tagging between early and late long-term potentiation-induced synapses

2011 Fiscal Year Final Research Report

• Project/Area Number: 20300128
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Nara Institute of Science and Technology
• Principal Investigator: SHIOSAKA Sadao 奈良先端科学技術大学院大学, バイオサイエンス研究科, 教授 (90127233)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Shigetaka 旭川医科大学, 医学部, 教授 (20230740)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Yasuyuki 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (90346320) ; TAMURA Hideki 奈良先端科学技術大学院大学, バイオサイエンス研究科, 助教 (80437516)
• Project Period (FY): 2008 – 2011
• Keywords: ニューロプシン(KLK8) / 海馬シャーファー側枝 / 海馬CA1 / LTP / 受容体蛋白質 / NMDA受容体 / Synaptic tagging

Research Abstract

Accumulating evidence has suggested pivotal roles for neural proteases in cognitive functions. Among such proteases, neuropsin, a kallikrein gene-related(KLK) endoprotease, appears to have a significant plasticity function that has been analyzed primarily in the hippocampal Schaffer-collateral pathway. Enzymatically active neuropsin is necessary to establish the early phase of long-term potentiation(LTP). Associations between early and persistent-LTP synapses may be related to mammalian working memory and consequently integration in learning and memory(Ishikawa et al). We challenged and succeeded to obtaining specific substrate for protease neuropsin and found that neuregulin-1 is the most suitable native substrate for neuropsin(Tamura et al). Novel signaling pathway of neuropsin-neuregulin might be a significant in mammalian cognition.

Research Products

• [Journal Article] Neuropsin-a possible early phase synaptic mediator (2011)
  • Author(s): SHIOSAKA, S. & ISHIKAWA, Y
  • Journal Title: J. Chem. Neuroanat Volume: 42 Pages: 24-29
• [Journal Article] Neuropsin cleaves EphB2 in the amygdala to control anxiety (2011)
  • Author(s): ATTWOOD, B. K., BOURGOGNON, J. M., PATEL, S., MUCHA, M., SCHIAVON, E., SKRZYPIEC, A. E., YOUNG, K. W., SHIOSAKA, S., KOROSTYNSKI, M., PIECHOTA, M., PRZEWLOCKI, R. & PAWLAK, R
  • Journal Title: Nature Volume: 473 Pages: 372-375
• [Journal Article] Diversity of Neuropsin(Kallikrein8)-dependent Synaptic Associativity in the Hippocampal Pyramidal Neuron (2011)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Journal Title: Journal of Physiology[London] Volume: 589 Pages: 3559-3573
• [Journal Article] Molecular mechanism of kallikrein-related peptidase 8/neuropsin-induced hyperkeratosis in inflamed skin (2010)
  • Author(s): SHINGAKI, K., MATSUZAKI, S., TANIGUCHI, M., KUBO, T., FUJIWARA, T., KANAZAWA, S., YAMAMOTO, A., TAMURA, H., MAEDA, T., OOI, K., MATSUMOTO, K., SHIOSAKA, S. & TOHYAMA, M
  • Journal Title: Br. J. Dermatol Volume: 163 Pages: 466-475
• [Journal Article] Olig2-expressing progenitor cells preferentially differentiate into oligodendrocytes in cuprizone-induced demyelinated lesions (2009)
  • Author(s): ISLAM, M. S., TATSUMI, K., OKUDA, H., SHIOSAKA, S. & WANAKA, A
  • Journal Title: Neuroc hem. Int Volume: 54 Pages: 192-198
• [Journal Article] Acute stress increases neuropsin mRNA expression in the mouse hippocampus through the glucocorticoid pathway (2008)
  • Author(s): HARADA, A., SHIOSAKA, S., ISHIKAWA, Y. & KOMAI, S
  • Journal Title: Neurosci. Lett Volume: 436 Pages: 273-277
• [Journal Article] Increased anxiety-like behavior in neuropsin(kallikrein-related peptidase8) genedeficient mice (2008)
  • Author(s): HORII, Y., YAMASAKI, N., MIYAKAWA, T. & SHIOSAKA, S
  • Journal Title: Behav. Neurosci Volume: 122 Pages: 498-504
• [Journal Article] Neuropsin(KLK8)-dependent and-independent synaptic tagging in the Schaffer-collateral pathway of mouse hippocampus (2008)
  • Author(s): ISHIKAWA, Y., HORII, Y., TAMURA, H. & SHIOSAKA, S
  • Journal Title: J. Neurosci Volume: 28 Pages: 843-849
• [Journal Article] Genetic variations of human neuropsin gene and psychiatric disorders : polymorphism screening and possible association with bipolar disorder and cognitive functions (2008)
  • Author(s): IZUMI, A., IIJIMA, Y., NOGUCHI, H., NUMAKAWA, T., OKADA, T., HORI, H., KATO, T., TATSUMI, M., KOSUGA, A., KAMIJIMA, K., ASADA, T., ARIMA, K., SAITOH, O., SHIOSAKA, S. & KUNUGI, H
  • Journal Title: Neuropsychopharm Volume: 33 Pages: 3237-3245
• [Journal Article] Integrated In vivo Neural Imaging and Interface CMOS Devices : Design, Packaging, and Implementation (2008)
  • Author(s): NG, D. C., NAKAGAWA, T., MIZUNO, T., TOKUDA, T., NUNOSHITA, M., TAMURA, H., ISHIKAWA, Y., SHIOSAKA, S. & OHTA, H
  • Journal Title: IEEE Sensor J Volume: 8 Pages: 121-130
• [Journal Article] One-chip sensing device(biomedical photonic LSI) enabled to assess hippocampal steep and gradual up-regulated proteolytic activities (2008)
  • Author(s): TAMURA, H., NG, D. C., TOKUDA, T., NAOKI, H., NAKAGAWA, T., MIZUNO, T., HATANAKA, Y., ISHIKAWA, Y., OHTA, J. & SHIOSAKA, S
  • Journal Title: J. Neurosci. Meth Volume: 173 Pages: 114-120
• [Presentation] Neuropsin(KLK8)シグナル系-精神疾患の新規治療戦略への期待 (2012)
  • Author(s): 塩坂貞夫
  • Organizer: 大阪神経科学研究会(ORIGIN)
  • Place of Presentation: 大阪
  • Year and Date: 20120300
• [Presentation] 海馬におけるニューロプシン依存的シナプス連合性の解析 (2011)
  • Author(s): 石川保幸、田村英紀、塩坂貞夫
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 金沢
  • Year and Date: 20110000
• [Presentation] 自由行動下マウスの海馬CA1におけるニューロプシン依存的シナプス可塑性 (2011)
  • Author(s): 山下春奈、石川保幸、塩坂貞夫
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 金沢
  • Year and Date: 20110000
• [Presentation] マウス海馬におけるマトリックスメタロプロテアーゼ活性の組織学的解析 (2011)
  • Author(s): 鈴木春満、金河大、塩坂貞夫
  • Organizer: 第54回日本神経化学会大会
  • Place of Presentation: 金沢
  • Year and Date: 20110000
• [Presentation] ニューロプシン・ニューレグリンシステムの脳内分布と機能 (2011)
  • Author(s): 河田美穂、田村英紀、塩坂貞夫
  • Organizer: 第87回日本解剖学会近畿支部学術集会
  • Place of Presentation: 兵庫
  • Year and Date: 20110000
• [Presentation] 新奇環境はシナプス可塑性に関与するプロテアーゼ、ニューロプシン(klk8)の遺伝子発現を高める (2011)
  • Author(s): 金河大、鈴木春満、畠中由美子、石川保幸、塩坂貞夫
  • Organizer: 第88回生理学会第116回解剖学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20110000
• [Presentation] Chemical LTP刺激によってシナプス膜に集積する分子のスクリーニング (2011)
  • Author(s): 中村雪子、石川保幸、塩坂貞夫
  • Organizer: 第88回生理学会第116回解剖学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 20110000
• [Presentation] Novel environment increases plasticity-related protease neuropsin gene without change in tPA gene ISN-ESN (2011)
  • Author(s): KANAGAWA, D., ISHIKAWA, Y., & SHIOSAKA, S
  • Organizer: 23rd Biennial Meeting
  • Place of Presentation: Athens, Greece
  • Year and Date: 20110000
• [Presentation] Histological profile of synaptic matrix metalloproteinase activity in the mouse hippocampus (2011)
  • Author(s): SUZUKI, H., KANAGAWA, D., & SHIOSAKA, S.
  • Organizer: 23rd Biennial Meeting
  • Place of Presentation: Athens, Greece
  • Year and Date: 20110000
• [Presentation] Functional neuroimaging by using an implantable CMOS multimodal device in a freely-moving mouse (2011)
  • Author(s): Kobayashi, T., TAMURA, H. HATANAKA, Y., MOTOYAMA, M., NODA, T., SASAGAWA, K., TOKUDA, T., ISHIKAWA, Y., SHIOSAKA, S. OHTA, J.
  • Organizer: Biomedical Circuits and Systems Conference(BioCAS)
  • Place of Presentation: IEEE
  • Year and Date: 20110000
• [Presentation] Diversity of neuropsin-dependent synaptic associativity (2011)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: Society for Neuroscience
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 20110000
• [Presentation] Neuropsin dependent synaptic tagging in mouse hippocampus (2010)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: Society for Neuroscience
  • Place of Presentation: San Diego, USA
  • Year and Date: 20100000
• [Presentation] 細胞外セリンプロテアーゼニューロプシンの基質探索 (2010)
  • Author(s): 田村英紀、濱口晴也、石川保幸、塩坂貞夫
  • Organizer: 第53回日本神経化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20100000
• [Presentation] ニューロプシン依存的シナプスタギングの解析 (2010)
  • Author(s): 石川保幸、田村英紀、塩坂貞夫
  • Organizer: 第53回日本神経化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 20100000
• [Presentation] Neuropsin dependent compartment specific and process specific synaptic tagging (2009)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 20090000
• [Presentation] Neuropsin dependent compartment specific and process specific synaptic tagging (2009)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: 第32回日本神経科学会
  • Place of Presentation: 名古屋
  • Year and Date: 20090000
• [Presentation] Real-time in vivo molecular quantification for freely-moving mouse's hippocampus (2009)
  • Author(s): TAMURA, H. HATANAKA, Y., MINAMI, H., TAGAWA, A., NODA, T., SASAGAWA, K., TOKUDA, T., OHTA, J., ISHIKAWA, Y., SHIOSAKA, S
  • Organizer: 第32回日本神経科学会
  • Place of Presentation: 名古屋
  • Year and Date: 20090000
• [Presentation] Environmental enrichment enhances neuropsin mRNA in the hippocampus (2009)
  • Author(s): KANAGAWA, D., ISHIKAWA, Y., & SHIOSAKA, S
  • Organizer: 第32回日本神経科学会
  • Place of Presentation: 名古屋
  • Year and Date: 20090000
• [Presentation] Neuropsin(KLK8) dependent compartment specific and process specific synaptic tagging (2009)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: 第52回日本神経化学会大会
  • Place of Presentation: 伊香保、群馬
  • Year and Date: 20090000
• [Presentation] Neuropsin-dependent and-independent synaptic tagging (2008)
  • Author(s): ISHIKAWA, Y., TAMURA, H. & SHIOSAKA, S
  • Organizer: 第51回日本神経化学会大会
  • Place of Presentation: 富山
  • Year and Date: 20080000
• [Presentation] Neuropsin依存的・非依存的シナプスタギング (2008)
  • Author(s): 石川保幸、堀井洋一郎、田村英紀、塩坂貞夫
  • Organizer: 第31回日本神経科学会
  • Place of Presentation: 東京
  • Year and Date: 20080000
• [Remarks] ホームページ
  • URL: http://bsw3.naist.jp/courses/courses205.html
• [Patent(Industrial Property Rights)] ニューレグリン-1(Neuregulin-1)部分ペプチド (2011)
  • Inventor(s): 塩坂貞夫、田村英紀
  • Industrial Property Rights Holder: 奈良先端科学技術大学院大学
  • Industrial Property Number: 特許、特願2011-259056
  • Filing Date: 2011-11-28