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Development of gene-therapy system for psychiatric disorders by mutagenesis DREADDs

Research Project

Project/Area Number 25660258
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Integrative animal science
Research InstitutionAzabu University

Principal Investigator

KIKUSUI Takefumi  麻布大学, 獣医学部, 教授 (90302596)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords前頭葉 / 扁桃体 / 不安 / DREADDs / FKBP5 / ウイルスベクター / Dreadds / マウス / ウィルスベクター / 不安行動 / エピジェネティクス
Outline of Final Research Achievements

DREADDs is artificially expressed receptor system activated by CNO, but not endogenous ligands, and this new technology that enables to control circuit specific or molecular specific modification of neural activity. Using this technic, we challenged to ameliorate depressive/anxiety symptoms in our mouse model by assessing behavior and molecular changes. First, we developed a new AAV retro-transport vector which express CRE, and we used double infections of AAV and successfully introduced DREADDs in the PFC-amygdala circuit. When these mouse were injected with CNO, their anxiety behavior decreased (15 out of 25). In addition, FKBP5, a chaperone protein for glucocorticoid receptor, were increased in the PFC of the early-weaned mice. In addition, the expression level of FKBP5 was negatively correlated with the anxiety level, suggesting that this molecular is responsible for the higher anxiety in the early weaned mice.

Report

(3 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (16 results)

All 2015 2014 2013 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (8 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] Genetic dissection of pheromone processing reveals main olfactory system-mediated social behaviors in mice2015

    • Author(s)
      Matsuo T, Hattori T, Asaba A, Inoue N, Kanomata N, Kikusui T, Kobayakawa R, Kobayakawa K.
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 112(3) Issue: 3 Pages: 88-92

    • DOI

      10.1073/pnas.1416723112

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Impairment of interstrain social recognition during territorial aggressive behavior in oxytocin receptor-null mice.2015

    • Author(s)
      Tatsuya Hattori, Kouta Kanno, Miho Nagasawa, Katsuhiko Nishimori, Kazutaka Mogi, and Takefumi Kikusui.
    • Journal Title

      Neuroscience Research

      Volume: 90 Pages: 90-94

    • DOI

      10.1016/j.neures.2014.05.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Sex differences in spatiotemporal expression of AR, ERα, and ERβ mRNA in the perinatal mouse brain.2014

    • Author(s)
      Kazutaka Mogi, Haruka Takanashi, Miho Nagasawa, and Takefumi Kikusui
    • Journal Title

      Neuroscience Letters

      Volume: 584 Pages: 88-92

    • DOI

      10.1016/j.neulet.2014.10.028

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] IL1RAPL1 knockout mice show learning deficiency, memory decline, hyperactivity and reduced anxiety-like behaviours.2014

    • Author(s)
      Misato Yasumura, Tomoyuki Yoshida, Maya Yamazaki, Manabu Abe, Rie Natsume, Kouta Kanno, Takeshi Uemura, Keizo Takao, Kenji Sakimura, Takefumi Kikusui, Tsuyoshi Miyakawa, Masayoshi Mishina
    • Journal Title

      Scientific Reports

      Volume: 4: 6613 Issue: 1 Pages: 6613-6613

    • DOI

      10.1038/srep06613

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sexual attractiveness of male chemicals and vocalizations in mice2014

    • Author(s)
      Asaba A, Hattori T, Mogi K, Kikusui T
    • Journal Title

      Frontiers in neuroscience

      Volume: 8:231 Pages: 231-231

    • DOI

      10.3389/fnins.2014.00231

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Organizational effects of estrogen on male-type vulnerability to early weaning.2013

    • Author(s)
      Kikusui T, Shimokawa Y, Kanbara N, Nagasawa M, Mogi K.
    • Journal Title

      Hormones and Behavior

      Volume: 64 Issue: 1 Pages: 37-43

    • DOI

      10.1016/j.yhbeh.2013.04.007

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Testosterone regulations on male sexual behavior and emission of ultrasounds in mice2014

    • Author(s)
      T. Kikusui. K. Mogi,
    • Organizer
      The International Congress of Neuroendocrinology 2014 including the 18th Annual Meeting of the Society for Behavioural Neuroendocrinology
    • Place of Presentation
      Sydney
    • Year and Date
      2014-08-17 – 2014-08-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Neonatal oxytocin treatments recover social deficits in oxytocin knock-out mice2014

    • Author(s)
      K. Mogi, T. Kikusui
    • Organizer
      The International Congress of Neuroendocrinology 2014 including the 18th Annual Meeting of the Society for Behavioural Neuroendocrinology
    • Place of Presentation
      Sydney
    • Year and Date
      2014-08-17 – 2014-08-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Basic relations among song and behavioral parameters2014

    • Author(s)
      K. Kanno and T. Kikusui
    • Organizer
      Workshop on Ultrasonic Communication in Rodents
    • Place of Presentation
      東京大学
    • Year and Date
      2014-08-04 – 2014-08-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Developmental imprinting of female preference for male song and its’ neuroendocrine effect in mice2014

    • Author(s)
      A. Asaba, K. Mogi, T. Kikusui
    • Organizer
      Workshop on Ultrasonic Communication in Rodents
    • Place of Presentation
      東京大学
    • Year and Date
      2014-08-04 – 2014-08-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] Chemical and auditory senses regulate mice social behavior.2013

    • Author(s)
      Kikusui T.
    • Organizer
      Neuro2013
    • Place of Presentation
      京都国際会議場
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 早期離乳が C57BL/6系マウスの恐怖記憶制御と母性行動に与える影響2013

    • Author(s)
      石田結子、永澤美保、茂木一孝、菊水健史
    • Organizer
      日本行動神経内分泌研究会
    • Place of Presentation
      鹿児島市
    • Related Report
      2013 Research-status Report
  • [Presentation] 早期離乳と児への影響2013

    • Author(s)
      菊水健史
    • Organizer
      日本周産期・新生児医学会学術集会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] オキシトシンの社会機能:個体認知から絆形成、そしてストレス緩衝作用2013

    • Author(s)
      菊水健史
    • Organizer
      プライマルヘルスケア学会
    • Place of Presentation
      鎌倉市
    • Related Report
      2013 Research-status Report
    • Invited
  • [Remarks] 研究室HPTopics

    • URL

      https://sites.google.com/a/carazabu.com/car/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://azabu.carazabu.com/car/topics

    • Related Report
      2013 Research-status Report

URL: 

Published: 2014-07-25   Modified: 2019-07-29  

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