Researchers Database

IWASAKI Shinichi

    Graduate School of Medical Sciences Department of Otolaryngology, Head and Neck Surgery Professor
Last Updated :2021/06/11

Researcher Information

J-Global ID

Research Interests

  • めまい・平衡医学   神経耳科学   耳科学   

Research Areas

  • Life sciences / Otorhinolaryngology

Published Papers

Research Grants & Projects

  • 透明化手法を用いた新規イメージング技術による内耳病態の包括的・網羅的解析
    日本学術振興会:科学研究費助成事業 基盤研究(A)
    Date (from‐to) : 2020/04 -2024/03 
    Author : 山岨 達也; 岩崎 真一; 木下 淳; 樫尾 明憲; 鴨頭 輝; 近藤 健二; 藤本 千里; 浦田 真次; 松本 有
  • Investigation of the role of necroptosis in the inner ear diseases and its application for treatments
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2018/04 -2021/03 
    Author : 岩崎 真一; 吉川 弥生; 樫尾 明憲; 藤本 千里
     
    生後3日の幼若マウスより摘出した蝸牛の器官培養を用いて、ゲンタマイシンを様々な濃度で投与することで、有毛細胞障害を引き起こし、免疫染色を用いて、アポトーシスとネクローシスおよびネクロプトーシスの誘導についての解析を行った。 第一段階として、Propidium iodide (PI)の核染色を、myosin7aによる有毛細胞染色と、DAPIによる核染色とともに行い、様々な濃度のゲンタマイシンを投与し、アポトーシスとネクローシスについての全体的な評価を行った。 ゲンタマイシンによる有毛細胞障害は、ゲンタマイシンの濃度および時間依存的に変化し、0.3-1mMの濃度で24時間以上培養を行うことで、統計学的に有意な有毛細胞障害が、外有毛細胞および内有毛細胞ともに認められた。 PIによる核染色では、内有毛細胞では、障害の6時間後にはネクローシスを示唆する核の膨化を認め、24時間後にはアポトーシスを示唆する核の濃縮を認めた。外有毛細胞でも、障害の12時間後では、核の膨化が優位で、24時間後では核の濃縮が主に認められ、内有毛細胞と同様の傾向を認めた。 引き続き、ネクロプトーシスのマーカーである、RIP1, RIP3, MLKLの免疫染色については、染色がうまくいかないため、ポジティブコントロールである、肝臓、および腎臓を用いて、条件について現在検討中である。
  • Integrated understanding of plastic alteration of vestibular system and countermeasures for adaptive disorder
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
    Date (from‐to) : 2015/06 -2020/03 
    Author : 森田 啓之; 梶 博史; 上田 陽一; 岩崎 真一; 村谷 匡史
     
    ①重力変化に応答する遺伝子の役割:微小重力により耳石器で発現が低下したEnpepのKOマウスを作製したが,表現型として平衡機能障害等は見られなかった。 ②前庭系可塑的変化の中枢経路:重力環境変化で発現が変化した前庭神経核GABA受容体,グルタミン酸受容体の機能をphotogenetics,chemogenetics手法を用いて検討した。グルタミン酸受容体刺激では同側に,GABA受容体刺激では対側に体が傾いた。また,両側グルタミン酸受容体刺激では著明な深部体温低下がみられ,重力環境変化により引き起こされる平衡機能障害・深部体温低下に前庭神経核のこれらの受容体が関与していることが示唆された。 ③重力変化が筋・骨連関および代謝調節に及ぼす影響:高脂肪高ショ糖食誘導性の体重増加,脂肪量増加,血糖上昇,耐糖能異常は前庭破壊により有意に改善され,さらにβ阻害薬およびトレッドミル運動負荷によっても有意に改善された。これらより,前庭系は自律神経系と運動系を介して,食餌誘導性の肥満とそれに続く糖代謝異常に影響を及ぼす可能性が示唆された。 ④長期宇宙滞在により引き起こされる耳石前庭機能障害とその対策:長期宇宙滞在前後でcVEMP (球形嚢機能) とoVEMP (卵形嚢機能) 検査を実施し,帰還直後に球形嚢機能の著明な低下が起こり,閉眼起立時の重心動揺が大きくなることが分かった。また,noisy-GVSにより重心動揺の増大が抑制されることから,帰還後の平衡機能障害の対策としてのnoisy-GVSの有効性が示唆された。 ⑤経皮的noisy-GVSによる前庭系可塑性の誘導に基づくバランス障害改善効果の検討:二重盲検ランダム化プラセボ対照クロスオーバー試験(医師主導治験)を計画し,PMDAによる承認,IRB申請,治験計画届の提出を済ませ,平成31年2月より被験者の組み入れを開始した。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research
    Date (from‐to) : 2015/04 -2018/03 
    Author : Iwasaki Shinichi
     
    To evaluate peripheral vestibular function in experimental animals, we have developed a system to record short -latency vestibular evoked potential (VsEP). In this system, we adopted newly developed vibrator and motor to provide linear and angular accelerations, respectively. We could record reliable and repeatable VsEPs in response to linear accelerations of the head in mice. The waveforms of VsEP were different from auditory brainstem responses (ABRs). In mice treated with ototoxic drugs, kanamycin and ethacrynic acids, ABRs were absent, but VsEPs could be recorded. In contrast, in mice whose inner ears were surgically damage, both ABRs and VsEPs were absent. These results suggested that VsEPs evoked by linear acceleration were originated from the vestibular endorgans, probably the otolith organs. On the other hand, we could not record reliable VsEPs in response to angular accelerations, probably due to insufficient power of the rotatory motor that we used to evoke VsEPs.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2014/04 -2018/03 
    Author : SUZUKI Mitsuya
     
    As compared to that in the non-ovariectomized group (control) the ABR threshold in the ovariectomized group was significantly higher at 32 KHz at 1 month after surgery (3-months-old), and at 2, 4, 8, 16, and 32 kHz at 2 months after surgery (4-months-old). 2) The three-layer structure which consists of laminae rarae eterna and interna and lamina densa, could be not identified clearly in the capillary basement membrane in the stria vascularis at both 3-months-old and 4-months-old in both the ovariectomized group and non-ovariectomized group. Distribution of cationic polyethyleneimine (PEI) particles was hardly observed on the capillary basement membranes in the stria vascularis in both the ovariectomized group and control group. 3) No marked difference in expression of ER alpha and ER beta was observed in the cochlea between the control group and the ovariectomized group.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2014/04 -2017/03 
    Author : Yamasoba Tatsuya
     
    When endogenous antioxidant MnSOD was reduced to half, oxidation stress of the cochlea was exacerbated by aging and acoustic trauma aggravated it. When GeO2 was given to mice, cochlear tissue showed marked degeneration with decrease of mitochondrial function. This damage was ameliorated by antioxidant. When gentamycin was injected into the middle ear, hair cell(HC) in semicircular canal showed marked degeneration and showed partial recovery due to regeneration via cell division of the sopporting cells. When TrkB agonist was given, HC showed significant recovery and synapse and afferent fibers were better preserved. When immortalized inner ear cells were exposed to oxidation stress, mitochondria were degenerated, mitochondrial membrane potential decreased, mitochondrial fusion/fission was impaired, and respiratory capacity was affected. We found that the cochlear HC, possess autophagy functoion. When Atg5 was knock out in the cochlear HC, these cells exhibited progressive degeneration.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2013/04 -2017/03 
    Author : Iwasaki Shinichi
     
    To investigate the role of the intracellular proteolysis systems in damages in the inner ear, we analyzed the roles of the ubiquitin-proteasome system and the autophagy-lysosome system. To investigate the role of the autophagy-lysosome system in the inner ear, we generated mice deficient in a gene essential for autophagy (Atg5) in hair cells in the inner ear. Deletion of Atg5 resulted in hair cell degeneration and profound congenital hearing loss. To investigate the role of the ubiquitin-proteasome system in the inner ear, we analyzed the effect of proteasome inhibitor (MG-132) in cultured inner ear cells under oxidative damage. The low concentration of proteasome inhibitor had some protective effect, but it had toxic effect in the higher concentration.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
    Date (from‐to) : 2011/04 -2014/03 
    Author : YAMASOBA TATSUYA; IWASAKI Shin-ichi; KIKKAWA Yayoi; SAKAMOTO Takashi; KASHIO Akinori; YASUI Takuya; PROLLA Tomas A.; SOMEYA Shin-ichi
     
    We investigated the association of oxidative stress and age-related hearing loss (AHL) using several transgenic mice in which the oxidative stress is enhanced or suppressed. We first examined whether reduction in manganese superoxide dismutase (Mn-SOD) accelerated AHL. At 16 months, immunoreactivity of 8-hydroxydeoxyguanosine was significantly greater in Mn-SOD heterozygous knockout (HET) mice compared to WT mice, but that of 4-hydroxynonenal did not differ between them. Age-related ABR threshold shifts and the extent of cochlear degeneration did not differ between WT and HET mice, suggesting that decrease of Mn-SOD by half increases oxidative stress in the cochlea to some extent but does not accelerate AHL. In contrast, glutathion reductase knockout mice exhibited acceleration of ABR threshold shifts at high frequencies, suggesting that oxidization of glutathione is crucial in the development of AHL.
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2010 -2012 
    Author : IWASAKI Shinichi
     
    To clarify the origin of ocular vestibular evoked myogenic potential (oVEMP), we performed experiments trying to record oVEMPs from guinea pigs. By inserting an electrode through lower eyelids and contacting it near extraocular muscles, we could record negative potentials with the peak latency of 3 msec. The potential was reduced by destruction of inner ear of the contralateral side, and was abolished by destruction of inner ears of both sides, suggesting that the response was dependent on the inner ears of both sides. Furthermore, by recoding directly from extraocular muscles, we confirmed that the oVEMPs in guinea pigs are originated from both the inferior oblique muscles and the inferior rectus muscles.
  • 起立性低血圧に伴うめまいの循環動態の評価と加圧トレーニングによる治療
    日本学術振興会:科学研究費助成事業 挑戦的萌芽研究
    Date (from‐to) : 2009 -2010 
    Author : 山岨 達也; 中島 敏明; 岩崎 真一
     
    高強度トレーニングは、活性酸素の産生を高め、酸化ストレスを亢進することが知られている。低強度加圧筋力トレーニングは、高強度トレーニングに匹敵する筋肥大効果をみとめると報告されており、起立性低血圧の治療に応用した。また加圧トレーニングならびに種々な運動様式の血中酸化ストレス指標に及ぼす影響につき健常人ならびに患者で検討した。各種目において、血中の酸化ストレス指標として活性酸素代謝産物濃度(dROMs test)と抗酸化力指標(BAP test)を測定した。加圧下での低負荷エルゴメーター運動及び筋力トレーニングは、非加圧時に比し、有意なdROMs、BAP上昇を認めた。さらに、健常人では、BAPは、乳酸、WBC、ノルアドレナリン(NOR)と有意な相関をみとめたが、dROMsとは相関は見られなかった。一方、起立性低血圧群では、dROMsは、乳酸、WBC、NORと有意な相関をみとめ、BAPも乳酸、WBCと相関を認めた。このように、加圧トレーニングでは、酸化ストレス・抗酸化力の亢進が見られた。健常人では、運動強度、血流制限に依存して抗酸化力が活性化し、酸化ストレスの上昇を抑制するが、疾患群では、運動強度、血流制限によって依存して酸化ストレスが亢進すると思われ、加圧トレーニングを応用する際には、負荷強度、血流制限の程度などを十分考慮する必要があると思われた。我々は、重篤な起立性低血圧患者においてマシンが使用できない場合は、elastic bandを用いた加圧トレーニング、加圧ウォークなどの負荷の軽い加圧トレーニングも実施している。そこで、高齢者の加圧ウォークの下肢筋力、筋肥大ならびにQOL改善効果についても検討した。加圧ウォークは、高齢者の下肢筋力を改善するとともに、静脈コンプライアンスを改善した。今後、起立性低血圧患者において、加圧トレーニングの効果とともに、安全で効果的なトレーニングメニューの作成につき、酸化ストレス、炎症の面からも研究を継続する予定である。
  • Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2007 -2008 
    Author : ITO Ken; IWASAKI Shinichi; SAHARA Yoshinori; SAHARA Yoshinori
     
    ラット前庭神経節細胞の細胞体にその末梢受容器(耳石器・半規管膨大部)を付着した標本を作成し、細胞生理学的実験を行う手法を確立した。培養方法としては、Leibovitz's L-15を使用した短時間(< 5hr)培養が最適であることが分かった。 生理学的実験 : 末梢前庭器-前庭神経細胞体を一体とする標本において、神経のパッチクランプ記録を行うことが可能となった。脱分極刺激(電流注入)による神経発火パターンを記録したところ、主にphasic typeの発火であり、今のところ単離・培養したものと大きな違いが無い結果となっている。同様の標本において前庭神経節細胞をパッチクランプして性質を調べた上でピペット内に予め入れておいたビオチンにより逆向性染色を行う実験は、パッチクランプの成功率が不十分で、また実験中に細胞が死んだりパッチが外れてしまうトラブルが多いことから未だ信頼に足る結果が得られていない。 免疫組織学的・分子生物学的実験 : 末梢前庭器-前庭神経細胞体を一体とする標本において、神経細胞の性質等を検索した後に細胞質を電極内に吸引し、Single Cell RT-PCRを行う実験は成功率が低く、その原因は単離細胞と異なり内容の吸引が難しいことであると分かった。未だ信頼性の高いデータとはなっていない。前庭神経節の興奮性の調節に関与すると分かったイオンチャネルやリガンド受容体の免疫染色については、試薬を購入して実験を開始したばかりの段階である。本研究のここまでの成果を踏まえて、今後も研究を継続する予定である。
  • A study on the physiological and pharmacological characteristics of vestibular ganglion cells
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2005 -2007 
    Author : IWASAKI Shinichi; ITO Ken
     
    In the present study, we have established the method of culture of primary vestibular ganglions surviving at least 4 days. We have examined the intrinsic firing properties of isolated rat vestibular ganglion cells (VGCs) and explored contributions of K^+ channels to the discharge regularity. Three classes of VGCs were distinguished on the basis of a degree of spike frequency adaptation observed during sustained membrane depolarization: most neurons exhibited a strong adaptation generating just a single spike or short bursts of spikes, and the others showed moderate adaptation or tonic firing. A degree of spike frequency adaptation in a neuron did not correlate with the cell size. Considerable variation in K^+ currents was present in the class of VGCs. In the presence of 4-aminopyridine or α-dendrotoxin (α-DTX), selective blockers of Kvl α subunits, phasic firing turned into sustained firing, indicating that Kvl channel control the firing characteristic of the pahsic VGCs. In tonic VGCs, tetraethylammonium decreased the frequency of discharges at membrane potentials above threshold while α-DTX lowered the threshold for initiation of discharge in response to depolarizing current steps. Blockade of Ca^<2+> activated K^+ channels and H- currents also had some effects on the firing pattern of the tonic VGCs. Our results indicate that VGCs have heterogeneous intrinsic firing properties, and that low-threshold K^+ channels are critical to determining a pattern of spike discharges that optimize the responsiveness of the vestibular neurons, thereby contributing to the timing of VG inputs.
  • Information processing in auditory space
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A)
    Date (from‐to) : 2003 -2006 
    Author : KAGA Kimitaka; YAMASOBA Tatsuya; ITO Ken; IWASAKI Shinichi; KARINO Shotaro; NAKANO Masayuki
     
    In order to illuminate auditory space, sound lateralization tests were performed to compare the magnet coil bone-conduction headphone with the giant magnetostrictive bone-conduction headphone using 18 healthy participants. Although, no significant difference between these bone-conduction headphones was obtained for the interaural time difference and interaural intensity difference, a significant difference was obtained for the time-intensity trade. This revealed that the difference between the headphone is apparent in the integration of the heterogeneous sensations of the time and intensity difference at the cognitive level, but no difference is apparent between the homogeneous sensations of the discrimination of interaural time difference or interoaural intensity difference at the sensory level. It was concluded that the difference of the giant magnetostrictive headphone. However, sound localization test using speakers' method in the aneic room revealed that auditory space of bone conduction is smaller than that of airconductive.
  • On the role of subtypes of muscarinic receptors in the inner ear
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2003 -2005 
    Author : ITO Ken; IWASAKI Shinichi; MATSUI Minoru
     
    This year, we continued our research on the basis of what we have established during the past two years. However, we encountered two troubles at the beginning of the year. First, because of epidemic problems, supply of the knock-out animals was disconnected for about half a year. The stable supply was re-established in November and we resumed the experiments. Secondly, in the meantime, a competing laboratory in the States reported that their mice lacking muscarinic receptors (product independent of our knock-outs) had almost normal hearing and similar susceptibility to ototoxic agents (Maison SF, et al. 2005). However, we made progress in two points. First, we revised the computer software to record OAEs, which was a pending problem from the last year, and enabled recording DPOAEs in animals as well as in humans. Secondly, considering the situation described above, we tried to shift the axis of our research in the inner ear from the auditory system to the vestibular system and finally were able to record action potentials of vestibular ganglion cells in rodents on the whole-cell patch clamp mode. We also revealed the expression of mRNAs for muscarinic receptors in vestibular ganglion cells by means of DNA arrays. Planned studies in the near future : 1) We still continue the experiments on comparative studies on susceptibility to extraordinary noise and to ototoxic drugs using knock-out and wild-type mice. This is because the results may differ from those from the USA group, since the knock-out mice were independently produced. 2) Since the existence of muscarinic receptors on the vestibular ganglion cells in rodents was indicated, we plan first to investigate modulation of excitability of neurons by muscarinic receptors and then to reveal the difference of neuronal firing patterns between knock-out and wild-type mice. Moreover, by investigating the difference in contribution of ionic channels on action potential formation, the contribution of muscarinic receptors to developmental processes of vestibular ganglion cells will be deduced.
  • 内耳支持細胞におけるギャップジャンクションの生理学的機能についての基礎的研究
    日本学術振興会:科学研究費助成事業 若手研究(B)
    Date (from‐to) : 2003 -2004 
    Author : 岩崎 真一
     
    昨年度の研究で、モルモットの単離ダイテルス細胞の膜電流は主にカリウム電流で厚生されており、その大部分は電位依存性カリウムチャンネルのブロッカーであるテトラエチルアンモニウム(TEA)によりブロックされることを明らかにした。 本年度はペアになったダイテルス細胞を使用し、膜容量の測定を行うことで、ギャップジャンクションの薬理学的特性を調べた。ペアになったダイテルス細胞の膜容量はギャップジャンクションのブロッカーである、カルベノキソロンの投与により、約半分に減少した。このことは、ダイテルス細胞間の結合が主にベノキソロン感受性のギャップジャンクションによって結合していることを意味する。別のギャップジャンクションブロッカーであるオクタノールの投与によっても同様の結果が得られた。しかしながら、1回の実験において、ペアになったダイテルス細胞は非常に少数であり、データを効率よく得るのは容易ではなかった。また、ギャップジャンクションに影響を与えることが知られているアミノ配糖体や一酸化窒素の阻害薬の効果も試してはみたが、はっきりとした薬剤の効果をみるには至らなかった。 複数のダイテルス細胞のうち、隣接する2つのダイテルス細胞に対して、それぞれの細胞よりホールセルを記録し、そのコンダクタンスを調べる実験も試みたが、1つの細胞ではホールセル記録を行えるものの、2つの細胞で同時にホールセル記録を行うのは非常に確率が低く、その特性を検討するには至らなかった。
  • Physiological study of responses of vestibular afferents to short duration extracranial galvanic stiunulation
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2004 
    Author : TAKAI Yoshinari; IWASAKI Shin-ichi; USHIO Munetaka; TAKAHIRO Asakage
     
    We performed physiological studies concerning responses of vestibular afferents to short duration extracranial galvanic stimulation in guinea pigs and humans. In guinea pigs, some primary vestibular afferents responded to short duration extracranial galvanic stimulation. In human, short duration extracranial galvanic stimulation caused responses on the sternocleidomastoid mascle. The threshold of this response was 2.5mA and 5Hz was the optimal stimulation rate. Clinical studies suggested that this response is of vstibular origin. And, it was revealed that this response is useful for the differential diagnosis of the nerve lesion from the endrorgan lesion.
  • The trial of inner hair cell injury by double patch clamp
    Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
    Date (from‐to) : 2001 -2003 
    Author : SUGASAWA Masashi; ITO Ken; IWASAKI Shinichi; SAKAMOTO Takashi
     
    Recently, Patch clamp techniques have been introduced into hair cell electrophysiological researches. By the way, mechanically and enzymatic ally isolation of hair cells from organ of Corti is necessary for patch clamp of hair cells. To purpose of this study is to clarify factors of cell injuries in the isolation process and to prevent those injuries. Finally rebuilding of normal environment of inner hair cell by double patch is a last purpose. Two indexes of the cell injuries became clear, vacuolation and resting membrane potential. The vacuolation at base occurs in almost all cells after isolation process. The cells without vacuolation showed good behavior during experiment. Other factor was resting membrane potential. The cells whose resting membrane potential was below -6OmV also showed good behavior during experiment. By using these indexes, we tried to prevent cell injures by changing isolation processes but all trials were in vain. It is impossible to reconstruct normal condition of inner hair cells by double patch because of rigidity of upper surface of inner hair cells. We could not make a seal on upper surface of inner hair cells. Another methodology is necessary for keeping inner hair cell condition in experiment.
  • 聴覚・前庭系の細胞生理学、めまい・平衡の臨床研究


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