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

• Project/Area Number: 24390366
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: Sapporo 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: ¥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.

Research Products

• [Journal Article] Effect of sevoflurane anesthesia on the comprehensive mRNA expression profile on the mouse hippocampus (2016)
  • Author(s): Hayase T, Tachibana S, Yamakage M.
  • Journal Title: Med Gas Res Volume: 6 Pages: 1-7
  • 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 Issue: 2 Pages: 369-377
  • DOI: 10.1097/aln.0000000000000949
  • 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
  • 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 Issue: 2 Pages: 410-417
  • DOI: 10.1213/ane.0000000000001063
  • 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 Issue: 10 Pages: 1148-1159
  • DOI: 10.1111/anae.13082
  • Peer Reviewed
• [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 Issue: 4 Pages: 627-630
  • DOI: 10.1007/s00540-015-1979-y
  • 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. (2014)
  • 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 Issue: 1 Pages: 1-5
  • DOI: 10.1097/ana.0000000000000149
  • 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 Issue: 12 Pages: 701-7
  • DOI: 10.1097/eja.0000000000000154
  • 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 Issue: 6 Pages: 2035-40
  • DOI: 10.3892/ol.2014.2046
  • 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 Issue: 2 Pages: 265-269
  • DOI: 10.3892/br.2013.210
  • 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: J Anesth Volume: Epub ahead of print Issue: 5 Pages: 696-701
  • DOI: 10.1007/s00540-014-1793-y
  • 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 Issue: 5 Pages: 1152-1159
  • DOI: 10.1097/aln.0000000000000160
  • 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 Issue: 4 Pages: 610-612
  • DOI: 10.1007/s00540-013-1751-0
  • 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
  • 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
  • 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 Issue: 6 Pages: 901-7
  • DOI: 10.1016/j.ajem.2011.06.013
  • Peer Reviewed
• [Journal Article] Pharmacokinetics and safety of 6 % hydroxyethyl starch 130/0.4 1n healthy malevolunteers of Japanese ethnicity after single infusion of 500 (2012)
  • Author(s): Yamakage M, Bepperling F, War genau M, Miyao H
  • Journal Title: J Anesth Volume: 26 Issue: 6 Pages: 851-7
  • DOI: 10.1007/s00540-012-1430-6
  • Peer Reviewed
• [Presentation] Elevation and Suppression of Paraoxon-induced Epileptic Activity in the Rat Hippocampus (2015)
  • 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
• [Presentation] Possible Mechanism of Neuroinflammation Induced by Surgical Procedure in the Mouse Hippocampus Determined by Using Transcriptome Analysis (2015)
  • 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
• [Presentation] Severity of Myasthenia Gravis Influences the Relationship Between TOF Ratio and Twitch Tension, and Run-down of Rat Endplate Potentials (2015)
  • 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
• [Presentation] Prediction of the Molecular Mechanism of Postoperative Nausea and Vomiting Using Transcriptome Analysis (2015)
  • 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
• [Presentation] Effects of Propofol and Sevoflurane on Heating-induced Tension Generation of Vascular Smooth Muscle in Rats (2015)
  • 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
• [Presentation] Estradiol Enhances Female Pica Behavior Through TACR1 Expression in the Caudate Putamen (2014)
  • 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
• [Presentation] Effect of Propofol on Vessel Tone After Cooling and Rewarming and Its Mechanism (2014)
  • 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
• [Presentation] Train of Four Ratios Cannot Reflect Muscle Strength in Severe Myasthenia Gravis: An In Vitro Study in a Rat Model of Experimenta (2014)
  • 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
• [Presentation] TACR1 Gene Polymorphism Is Associated With Gender Difference in Postoperative Nausea and Vomiting (2014)
  • 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
• [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 Amygdala (2014)
  • 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
• [Presentation] Phosphodiesterase 4 Inhibitor Roflumilast Improves the Bronchodilative Effect of Sevoflurane in Sensitized Airway (2013)
  • 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
• [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
• [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
• [Presentation] Bone Marrow-Derived Microglia That Express IL-1β Might Cause Negative Emotions Induced by Neuropathic Pain (2013)
  • 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
• [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
• [Presentation] The migration of bone marrow-derived microglia into the central nucleus of amygdala of neuropathic pain model following peripheral nerve injury (2012)
  • Author(s): Sawada A
  • Organizer: The annual meeting of the American Society of Anesthesiologists.
  • Place of Presentation: Washington, D.C.
• [Presentation] Haptotypes in human TACR1 gene are associated with postoperative nausea and vomiting (2012)
  • Author(s): Hayase T
  • Organizer: The annual meeting of the American Society of Anesthesiologists.
  • Place of Presentation: Washington, D.C.
• [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
• [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