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Determination of the molecular mechanism of volatile anesthetics using transcriptome analysis in thymo-cortico neurons of mice.

Research Project

Project/Area Number 24390366
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionSapporo Medical University

Principal Investigator

Yamakage Michiaki  札幌医科大学, 医学部, 教授 (70285005)

Co-Investigator(Kenkyū-buntansha) HAYASE TOMO  札幌医科大学, 医学部, 助教 (20579007)
杉野 繁一  札幌医科大学, 医学部, 助教 (00423765)
Project Period (FY) 2012-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2015: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2012: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsトランクスリプトーム / 麻酔科学
Outline of Final Research Achievements

We performed a transcriptome-wide association study, a total mRNA analysis, in the mouse brain to try to determine the molecular mechanism of volatile anesthetics. We also examined the behavior of mice to confirm the association between inhalation of volatile anesthetics and undesirable side effects such as nausea, vomiting, and cognitive dysfunction. Exposure to volatile anesthetics caused an increase in the expression level of the Rtn4rl2 gene in all mice and an increase in the expression level of the Lhx9 gene in aged mice. These results indicated that inhalation of volatile anesthetics causes neuroinflammation and induces apoptosis in juvenile mice. However, we did not find undesirable side effects of exposure to the volatile anesthetics in any of the mice. The results suggest that the mechanism by which exposure to volatile anesthetics causes nausea or cognitive dysfunction in mice is different from that in humans.

Report

(5 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • 2012 Annual Research Report

Research Products

(36 results)

All 2016 2015 2014 2013 2012

All Journal Article (17 results) (of which Peer Reviewed: 17 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (18 results) Book (1 results)

  • [Journal Article] Effect of sevoflurane anesthesia on the comprehensive mRNA expression profile on the mouse hippocampus2016

    • Author(s)
      Hayase T, Tachibana S, Yamakage M.
    • Journal Title

      Med Gas Res

      Volume: 6 Pages: 1-7

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Severity of Myasthenia Gravis Influences the Relationship between Train-of-four Ratio and Twitch Tension and Run-down of Rat Endplate Potentials.2016

    • Author(s)
      kazunobu takahashi
    • Journal Title

      Anesthesiology

      Volume: 124 Pages: 369-377

    • DOI

      10.1097/aln.0000000000000949

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The influence of depth of anesthesia on motor evoked potential response during awake craniotomy.2016

    • Author(s)
      Ohtaki S, Akiyama Y, Kanno A, Noshiro S, Hayase T, Yamakage M, Mikuni N.
    • Journal Title

      J Neurosurg

      Volume: 4 Pages: 1-6

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nitrite Reduces Ischemia-Induced Ventricular Arrhythmias by Attenuating Connexin 43 Dephosphorylation in Rats.2016

    • Author(s)
      Maruyama D, Hirata N, Tokinaga Y, Kawaguchi R, Yamakage M.
    • Journal Title

      Anesth Analg

      Volume: 122 Pages: 410-417

    • DOI

      10.1213/ane.0000000000001063

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficacy and Safety of a Lidocaine and Ropivacaine Mixture for Scalp Nerve Block and Local Infiltration Anesthesia in Patients Undergoing Awake Craniotomy.2016

    • Author(s)
      Chaki T, Sugino S, Janicki PK, Ishioka Y, Hatakeyama Y, Hayase T, Kaneuchi-Yamashita M, Kohri N, Yamakage M.
    • Journal Title

      J Neurosurg Anesthesiol

      Volume: epub Pages: 1-5

    • DOI

      10.1097/ana.0000000000000149

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] TACR1 gene polymorphism is associated with gender differences in postoperative nausea and vomiting.2015

    • Author(s)
      Hayase T, Sugino S, Moriya H, Yamakage M.
    • Journal Title

      Anaesthesia

      Volume: 70 Pages: 1148-1159

    • DOI

      10.1111/anae.13082

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Recovery of postoperative cognitive function in elderly patients after a long duration of desflurane anesthesia: a pilot study.2015

    • Author(s)
      Tachibana S, Hayase T, Osuda M, Kazuma S, Yamakage M.
    • Journal Title

      J Anesth

      Volume: epub Pages: 627-30

    • DOI

      10.1007/s00540-015-1979-y

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of bias in predicted and measured propofol concentrations during target-controlled infusions in obese Japanese patients: an open-label comparative study.2014

    • Author(s)
      Tachibana N, Niiyama Y, Yamakage M.
    • Journal Title

      Eur J Anaesthesiol

      Volume: 31 Pages: 701-7

    • DOI

      10.1097/eja.0000000000000154

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between the low-dose irinotecan regimen-induced occurrence of grade 4 neutropenia and genetic variants of UGT1A1 in patients with gynecological cancers.2014

    • Author(s)
      Moriya H, Saito K, Helsby N, Sugino S, Yamakage M, Sawaguchi T, Takasaki M, Kato H, Kurosawa N.
    • Journal Title

      Oncol Lett

      Volume: 7 Pages: 2035-40

    • DOI

      10.3892/ol.2014.2046

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single-nucleotide polymorphisms and copy number variations of the FCGR2A and FCGR3A genes in healthy Japanese subjects.2014

    • Author(s)
      Moriya H, Saito K, Helsby N, Hayashi N, Sugino S, Yamakage M, Sawaguchi T, Takasaki M, Takahashi M, Kurosawa N.
    • Journal Title

      Biomed Rep.

      Volume: 2 Pages: 265-269

    • DOI

      10.3892/br.2013.210

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of local infiltration analgesia for posterior knee pain after total knee arthroplasty: comparison with sciatic nerve block.2014

    • Author(s)
      Gi E, Yamauchi M, Yamakage M, Kikuchi C, Shimizu H, Okada Y, Kawamura S, Suzuki T.
    • Journal Title

      Journal of Anesthesia

      Volume: Epub ahead of print Pages: 696-701

    • DOI

      10.1007/s00540-014-1793-y

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphodiesterase 4 inhibitor roflumilast improves the bronchodilative effect of sevoflurane in sensitized airways.2014

    • Author(s)
      Zhou J, Iwasaki S, Yamakage M.
    • Journal Title

      Anesthesiology

      Volume: 120 Pages: 1152-1159

    • DOI

      10.1097/aln.0000000000000160

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of life-threatening hypercapnia with isoflurane in an infant with status asthmaticus.2013

    • Author(s)
      Masuda Y, Tatsumi H, Goto K, Imaizumi H, Yoshida SI, Kimijima T, Yamakage M.
    • Journal Title

      J Anesth

      Volume: Epub ahead of print

    • DOI

      10.1007/s00540-013-1751-0

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Substrate-dependent modulation of oxidative phosphorylation in isolated mitochondria following in vitro hypoxia and reoxygenation injury.2013

    • Author(s)
      Maruyama D, Hirata N, Miyashita R, Kawaguchi R, Yamakage M.
    • Journal Title

      Exp Clin Cardiol

      Volume: 18 Pages: 158-160

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 麻酔科学へのオミクス研究の導入と臨床麻酔での可能性2013

    • Author(s)
      杉野繁一, 早瀬知, 山蔭道明
    • Journal Title

      麻酔

      Volume: 62 Pages: 296-303

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pralidoxime inhibits paraoxon-induced depression of rocuronium-neurom uscular block in a time-dependent fashion.2012

    • Author(s)
      Narimatsu E, Niiya T, Takahashi K, Yamauchi M, Yamakage M
    • Journal Title

      Am J Emerg Med

      Volume: 30 Pages: 901-7

    • DOI

      10.1016/j.ajem.2011.06.013

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pharmacokinetics and safety of 6 % hydroxyethyl starch 130/0.4 1n healthy malevolunteers of Japanese ethnicity after single infusion of 5002012

    • Author(s)
      Yamakage M, Bepperling F, War genau M, Miyao H
    • Journal Title

      J Anesth

      Volume: 26 Pages: 851-7

    • DOI

      10.1007/s00540-012-1430-6

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Elevation and Suppression of Paraoxon-induced Epileptic Activity in the Rat Hippocampus2015

    • Author(s)
      Takada Y, Narimatsu E, Takahashi K, Niiya T, Yamakage M.
    • Organizer
      Anesthesiology annual meeting 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Possible Mechanism of Neuroinflammation Induced by Surgical Procedure in the Mouse Hippocampus Determined by Using Transcriptome Analysis2015

    • Author(s)
      Tachibana S, Hayase T, Yamakage M.
    • Organizer
      Anesthesiology annual meeting 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Severity of Myasthenia Gravis Influences the Relationship Between TOF Ratio and Twitch Tension, and Run-down of Rat Endplate Potentials2015

    • Author(s)
      Takahashi K, Niiya T, Narimatsu E, Yamakage M.
    • Organizer
      Anesthesiology annual meeting 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Prediction of the Molecular Mechanism of Postoperative Nausea and Vomiting Using Transcriptome Analysis2015

    • Author(s)
      Hayase T, Tachibana S, Yamakage M.
    • Organizer
      Anesthesiology annual meeting 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Effects of Propofol and Sevoflurane on Heating-induced Tension Generation of Vascular Smooth Muscle in Rats2015

    • Author(s)
      Kimizuka M, Takada Y, Tokinaga Y, Hayashi S, Kazuma S, Azumaguchi R, Yamakage M.
    • Organizer
      Anesthesiology annual meeting 2015
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2015-10-24
    • Related Report
      2015 Annual Research Report
  • [Presentation] Estradiol Enhances Female Pica Behavior Through TACR1 Expression in the Caudate Putamen2014

    • Author(s)
      Tomo Hayase, M.D., Shigekazu Sugino, M.D., Ph.D., Shun-suke Tachibana, M.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2014
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Effect of Propofol on Vessel Tone After Cooling and Rewarming and Its Mechanism2014

    • Author(s)
      Yasuyuki Tokinaga, M.D., Ph.D., Yukimasa Takada, M.D., Shunsuke Hayashi, none, Satoshi Kazuma, M.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2014
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Train of Four Ratios Cannot Reflect Muscle Strength in Severe Myasthenia Gravis: An In Vitro Study in a Rat Model of Experimenta2014

    • Author(s)
      Kazunobu Takahashi, M.D., Tomohisa Niiya, M.D., Ph.D., Eichi Narimatsu, M.D., Ph.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2014
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] TACR1 Gene Polymorphism Is Associated With Gender Difference in Postoperative Nausea and Vomiting2014

    • Author(s)
      Tomo Hayase, M.D., Shigekazu Sugino, M.D., Ph.D., Shun-suke Tachibana, M.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2014
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] An IL-1 Receptor Antagonist Improves Anxiety-Like Behavior Induced by Chronic Neuropathic Pain Via the Blockade of Phosphorylationof NMDA receptors on Neurons in the Amygdala2014

    • Author(s)
      Atsushi Sawada, M.D., Ph.D., Yukitoshi Niiyama, M.D., Ph.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2014
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2014-10-11 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] Phosphodiesterase 4 Inhibitor Roflumilast Improves the Bronchodilative Effect of Sevoflurane in Sensitized Airway2013

    • Author(s)
      Jing Zhou, M.D., Sohshi Iwasaki, M.D.,Ph.D., Michiaki Yamakage, M.D.,Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2013
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] Oprm1 Gene Polymorphism Reduces DNA Methylation at the Upstream CpG Island in Male Patients.2013

    • Author(s)
      Shigekazu Sugino, M.D.,Ph.D., Tomo Hayase, M.D., Misako Higuchi, M.D., Yuko Nawa, M.D.,Ph.D., Yukihiro Kumeta, M.D.,Ph.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2013
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] Recovery of Postoperative Cognitive Function in Elderly Patients After a Long Duration of Desflurane Anesthesia.2013

    • Author(s)
      Satoshi Kazuma, M.D., Tomo Hayase, M.D., Michiko Osuda, M.D., Shigekazu Sugino, M.D.,Ph.D., Michiaki Yamakage, M.D.,Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2013
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] Bone Marrow-Derived Microglia That Express IL-1β Might Cause Negative Emotions Induced by Neuropathic Pain2013

    • Author(s)
      Atsushi Sawada, M.D., Yukitoshi Niiyama, M.D.,Ph.D., Michiaki Yamakage, M.D.,Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2013
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] Mechanism of the Inhibitory Effect of Desflurane on Angiotensin II-Induced Vasoconstriction.2013

    • Author(s)
      Yasuyuki Tokinaga, M.D.,Ph.D., Yukimasa Takada, M.D., Shunsuke Hayashi, No Degree, Masayuki Akatsuka, M.D., Michiaki Yamakage, M.D., Ph.D.
    • Organizer
      American Society of Anesthesiologists Annual Meeting 2013
    • Place of Presentation
      San Francisco, U.S.A
    • Related Report
      2013 Annual Research Report
  • [Presentation] The migration of bone marrow-derived microglia into the central nucleus of amygdala of neuropathic pain model following peripheral nerve injury2012

    • Author(s)
      Sawada A
    • Organizer
      The annual meeting of the American Society of Anesthesiologists.
    • Place of Presentation
      Washington, D.C.
    • Related Report
      2012 Annual Research Report
  • [Presentation] Haptotypes in human TACR1 gene are associated with postoperative nausea and vomiting2012

    • Author(s)
      Hayase T
    • Organizer
      The annual meeting of the American Society of Anesthesiologists.
    • Place of Presentation
      Washington, D.C.
    • Related Report
      2012 Annual Research Report
  • [Presentation] デスフルラン:やはり覚醒の質は高かった2012

    • Author(s)
      山蔭道明
    • Organizer
      日本臨床麻酔学会第32回大会
    • Place of Presentation
      郡山
    • Related Report
      2012 Annual Research Report
  • [Book] 必携麻酔科初期研修マニュアル―3カ月麻酔科研修を充実したものとするために!2014

    • Author(s)
      山蔭 道明、枝長 充隆
    • Total Pages
      349
    • Publisher
      真興交易医書
    • Related Report
      2013 Annual Research Report

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Published: 2012-04-23   Modified: 2019-07-29  

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