Basic research for treatment of lower urinary tract dysfunction based on the brain mechanisms for stress-induced frequent urination
Project/Area Number |
20K07827
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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 52010:General internal medicine-related
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Research Institution | Kochi University |
Principal Investigator |
SHIMIZU Takahiro 高知大学, 教育研究部医療学系基礎医学部門, 准教授 (00363276)
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Co-Investigator(Kenkyū-buntansha) |
齊藤 源顕 高知大学, 教育研究部医療学系基礎医学部門, 教授 (60273893)
東 洋一郎 高知大学, 教育研究部医療学系基礎医学部門, 講師 (80380062)
清水 翔吾 高知大学, 教育研究部医療学系基礎医学部門, 助教 (90721853)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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Keywords | 脳 / ストレス / 排尿 / 下部尿路機能障害 / ニコチン受容体 / コルチコトロピン放出因子 / 硫化水素 / 一酸化炭素 / 頻尿 / 膀胱 / 膀胱機能 / GABA / 薬理学 / 脳・神経 / 排尿機能 |
Outline of Research at the Start |
「緊張するとトイレが近くなる」といった日常的な事象から、ストレスが排尿機能に何らかの影響を及ぼす事は想像に難くない。また軽度の心理・精神ストレスが頻尿症状を増悪させるとの報告もある。ストレスに対する生体反応は脳により制御されているが、ストレスが排尿機能へ及ぼす影響やストレスによる頻尿増悪の「脳内メカニズム」について詳細は未だ明らかではない。本研究では、排尿制御に関与する脳内分子に着目してストレスによる頻尿誘発のメカニズムを解明し、頻尿に対する新規治療薬開発の礎となる成果を挙げる事を目指す。
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Outline of Final Research Achievements |
Exposure to stress can affect urinary function, and lead to and exacerbate lower urinary tract dysfunctions (LUTD). The brain plays crucial roles in the regulation of the body’s responses to stress; however, it is still unclear how the brain integrates stress-related information to induce changes at multiple levels (lower urinary tract tissues, and peripheral and central nervous system), thereby affecting LUTD. In this study, we examined effects of brain molecules related to responses to stress [nicotinic acetylcholine receptor (nAChR) and corticotropin-releasing factor (CRF)] and brain gasotransmitters [hydrogen sulfide (H2S) and carbon monoxide (CO)] on urinary function in rats. We found that (1) brain α7 nAChRs can inhibit the micturition via brain GABAergic receptors, (2) brain CRF can facilitate the micturition via brain CRF1 and glutamatergic receptors, and that (3) brain H2S and CO can inhibit the micturition via brain GABAergic receptors.
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Academic Significance and Societal Importance of the Research Achievements |
ストレス曝露が頻尿誘発のみならず膀胱機能障害に伴う頻尿症状増悪に関与することが知られている一方、その機序をストレスを受容する脳に着目して解明した報告はほとんど無い。本研究により、これまで我々が同定したストレス反応制御に関わる脳内分子、nAChRおよびCRFがそれぞれ排尿抑制および排尿促進に関わること、さらに脳内ガス状伝達物質H2SおよびCOが排尿抑制に関与することが明らかとなった。本成果は、ストレス曝露により頻尿増悪が生ずる脳内機序解明のentry pointとなり、さらにはこれら脳内分子を標的としたストレス誘発性頻尿に対する新たな治療戦略構築に向けた基礎資料となることが期待される。
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Report
(4 results)
Research Products
(41 results)
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[Journal Article] A STRESS-RELATED NEUROPEPTIDE CORTICOTROPIN-RELEASING FACTOR INDUCES FACILITATION OF THE RAT MICTURITION THROUGH BRAIN GLUTAMATERGIC RECEPTORS2022
Author(s)
Shimizu T, Hata Y, Zou S, Yamamoto M, Shimizu Y, Ono H, Aratake T, Shimizu S, Higashi Y, Shimizu N, Karashima T, Saito M
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Journal Title
Continence
Volume: 2S2
Pages: 100319-100319
DOI
Related Report
Peer Reviewed
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[Journal Article] Stimulation of brain α7-nicotinic acetylcholine receptors suppresses the rat micturition through brain GABAergic receptors2021
Author(s)
Shimizu Y, Shimizu T, Zou S, Ono H, Hata Y, Yamamoto M, Aratake T, Shimizu S, Higashi Y, Karashima T, Saito M
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Journal Title
Biochem Biophys Res Commun
Volume: 548
Pages: 84-90
DOI
Related Report
Peer Reviewed
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[Journal Article] Stimulation of brain alpha7 nicotinic acetylcholine receptors can inhibit the rat micturition reflex through brain GABA receptors2020
Author(s)
Shimizu T, Shimizu Y, Ono H, Zou S, Yamamoto M, Hata Y, Aratake T, Shimizu S, Higashi Y, Honda M, Saito M
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Journal Title
Neurourol Urodyn
Volume: 39
Issue: S2
DOI
Related Report
Peer Reviewed
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[Presentation] Centrally administered corticotropin-releasing factor induces facilitation of the rat micturition via brain glutamatergic receptors2022
Author(s)
Shimizu T, Hata Y, Zou S, Yamamoto M, Ono H, Shimizu Y, Aratake T, Shimizu S, Higashi Y, Karashima T, Saito M
Organizer
American Urological Association 117th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] A stress-related neuropeptide corticotropin-releasing factor induces facilitation of the rat micturition through brain glutamatergic receptors2022
Author(s)
Shimizu T, Hata Y, Zou S, Yamamoto M, Shimizu Y, Ono H, Aratake T, Shimizu S, Higashi Y, Shimizu N, Karashima T, Saito M
Organizer
International Continence Society 52nd Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Brain α7 nicotinic acetylcholine receptors are involved in suppression of the rat micturition reflex via brain GABA receptors2021
Author(s)
Shimizu T, Shimizu Y, Zou S, Ono H, Hata Y, Yamamoto M, Aratake T, Shimizu S, Higashi Y, Karashima T, Honda M, Saito M
Organizer
American Urological Association 115th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Brain GABAA and GABAB receptors are involved in brain α7 nicotinic acetylcholine receptor-mediated inhibition of the rat micturition reflex2021
Author(s)
Shimizu T, Shimizu Y, Zou S, Ono H, Hata Y, Yamamoto M, Aratake T, Shimizu S, Higashi Y, Karashima T, Honda M, Saito M
Organizer
International Continence Society 51st Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Stimulation of brain alpha7 nicotinic acetylcholine receptors can inhibit the rat micturition reflex through brain GABA receptors2020
Author(s)
Shimizu T, Shimizu Y, Ono H, Zou S, Yamamoto M, Hata Y, Aratake T, Shimizu S, Higashi Y, Honda M, Saito M
Organizer
International Continence Society 50th Annual Meeting
Related Report
Int'l Joint Research
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[Presentation] Nitric oxide centrally induces facilitation of the rat micturition reflex through brain glutamatergic receptors2020
Author(s)
Ono H, Shimizu T, Zou S, Yamamoto M, Shimizu Y, Hata Y, Aratake T, Shimizu S, Higashi Y, Honda M, Saito M
Organizer
International Continence Society 50th Annual Meeting
Related Report
Int'l Joint Research
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