Cellular mechanisms of responses to hypoxia and hypercapnia in medullary neurons expressing a transcription factor, Phox2b
Project/Area Number |
19K06946
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 46030:Function of nervous system-related
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Research Institution | Showa University |
Principal Investigator |
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
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Keywords | 高炭酸ガス応答 / 低酸素応答 / Phox2b / チロシン水酸化酵素 / 吻側腹外側延髄 / 新生児ラット / PAR1 / アストロサイト / TFLLR / 孤束核 / カルシウムイメージング / Phox2b / 延髄 / 低酸素受容 / 高炭酸ガス受容 / チャネルロドプシン |
Outline of Research at the Start |
転写因子Phox2bは下位脳幹の自律神経ネットワークを構成する神経細胞に広く発現する.腹側延髄Phox2b発現細胞のサブグループ(チロシン水酸化酵素(TH)陰性細胞)は呼吸調節における高炭酸ガス中枢化学受容器細胞そのものであると考えられている.最近申請者はPhox2b陽性細胞の一部(TH陽性細胞)は低酸素に応答することを見出した.Phox2b陽性細胞は,背側延髄孤束核にも高密度で分布している.本研究では,延髄腹側および背側部に分布するPhox2b陽性細胞の機能,特に低酸素あるいは高炭酸ガス刺激に対する応答性,TH遺伝子発現との関連を明らかにし,さらにガス受容のイオン機構を明らかにする.
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Outline of Final Research Achievements |
We investigated membrane potential responses of cardio-respiratory neurons in the rostral ventrolateral medulla to hypoxic and hypercapnic stimulation in brainstem-spinal cord preparations from newborn rats. Responses were examined in the presence of TTX. Phox2b+/TH+ neurons indicated depolarization of 3.3 mV (n=15) in response to hypoxic stimulation but no significant change to hypercapnic stimulation. Phox2b+/TH- neurons did not respond to hypoxic stimulation but were depolarized by 6.1 mV (n=10) by hypercapnic stimulation. Membrane potential response of Phox2b-/TH- respiratory neurons to hypoxic stimulation varied; depolarization or hyperpolarization and the averaged change was -2.2 mV (n=19). The most noteworthy result in the present study is that Phox2b+/TH+ neurons (so called C1 adrenergic neurons) exhibited membrane depolarization as an intrinsic response to hypoxic stimulation, suggesting that they are central hypoxia-sensitive cells.
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Academic Significance and Societal Importance of the Research Achievements |
今回の特に注目すべき研究結果は,Phox2b+/TH+ニューロン(いわゆるC1アドレナリンニューロン)が低酸素刺激に直接脱分極応答を示し,中枢性低酸素受容細胞であることが明らかになったことである.低酸素応答の分子機構については今後の課題として残されている.一方,呼吸性ニューロン(Phox2b-/TH-)では低酸素刺激に対しては脱分極を示すものと過分極を示すものがあった.過分極応答にはKATPチャネルが関与すると考えられた.C1アドレナリンニューロンは交感神経活動維持に重要な役割を持つ一方で,中枢低酸素受容器として働くことが示唆されたことは意義深い.
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Report
(5 results)
Research Products
(36 results)
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[Journal Article] Novel oxygen sensing mechanism in the spinal cord involved in cardiorespiratory responses to hypoxia.2022
Author(s)
Barioni NO, Derakhshan F, Tenorio Lopes L, Onimaru H, Roy A, McDonald F, Scheibli E, Baghdadwala MI, Heidari N, Bharadia M, Ikeda K, Yazawa I, Okada Y, Harris MB, Dutschmann M, Wilson RJA.
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Journal Title
Sci Adv.
Volume: 8
Issue: 12
Pages: 1-21
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Optogenetic activation of DRN 5-HT neurons induced active wakefulness, not quiet wakefulness.2021
Author(s)
Moriya R, Kanamaru M, Okuma N, Yoshikawa A, Tanaka KF, Hokari S, Ohshima Y, Yamanaka A, Honma M, Onimaru H, Kikuchi T, Izumizaki M.
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Journal Title
Brain Res Bull.
Volume: 177
Pages: 129-142
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Structural and functional connectivity from the dorsomedial hypothalamus to the ventral medulla as a chronological amplifier of sympathetic outflow.2020
Author(s)
Kono Y, Yokota S, Fukushi I, Arima Y, Onimaru H, Okazaki S, Takeda K, Yazawa I, Yoshizawa M, Hasebe Y, Koizumi K, Pokorski M, Toda T, Sugita K, Okada Y.
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Journal Title
Sci Rep.
Volume: 10
Issue: 1
Pages: 13325-13325
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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