| 研究課題/領域番号 |
20K09898
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分57010:常態系口腔科学関連
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| 研究機関 | 松本歯科大学 |
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研究代表者 |
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| 研究分担者 |
安藤 宏 松本歯科大学, 歯学部, 准教授 (30312094)
北川 純一 松本歯科大学, 歯学部, 教授 (50373006)
海野 俊平 松本歯科大学, 歯学部, 講師 (80418920)
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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2022年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2021年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
2020年度: 1,040千円 (直接経費: 800千円、間接経費: 240千円)
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| キーワード | Swallowing Reflex / TRPA1 / TRPV4 / Swallowing reflex / Oropharyngeal dysphagia / Therapeutic targets |
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| 研究開始時の研究の概要 |
Difficulty in swallowing is a major health problem. We will investigate whether stimulation to the swallowing-related regions by natural products (e.g.; chemical extract from wasabi/mustard oil) can use as a treatment strategy to faciliate the triggering of swallowing and their undelying mechanism.
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| 研究実績の概要 |
In this project we investigate the involvement of TRPA1 and TRPV4 in swallowing reflex. We observed TRPA1 and TRPV4 expression on afferent neurons of the swallowing-related regions. TRPA1 localized majorly on small to medium diameter neurons and TRPV4 majorly localized on large to medium diameter neurons. We also observed that topical application of a chemical agonist for TRPA1, allyl isothiocyanate (AITC) or agonist for TRPV4, GSK1016790A, in the swallowing-related regions dose-dependently facilitated the triggering of swallowing reflex. Prior topical application of antagonists for TRPA1 or TRPV4 significantly reduced the AITC or GSK1016790A-induced swallowing reflex, respectively. Application of cold AITC (4 °C) very briefly reduced the on-site temperature to <17 °C (temperature at which TRPA1s can be activated), but had no effect on triggering of the reflex. By contrast, reducing the on-site temperature to <17 °C for a longer time by continuous flow of cold AITC or by application of iced AITC paradoxically delayed/prevented the triggering of AITC-induced reflexes. Prior application of the TRPA1 antagonist had no effect on the threshold for the punctate mechanical stimuli-induced reflex or the number of low-force or high-force continuous mechanical pressure stimuli-induced reflexes. We have published these data in "Scientific Reports" and "Front. Cell. Neurosci." journals. Now we are conducting research on the involvement of TRPV4 in water-induced swallowing reflex.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
Our research is progressing smoothly as planned. In previous fiscal years we conducted immunohistochemistry studies to understand the expression
profile of TRPA1 and TRPV4 in the SLN-innervated swallowing related-regions and in the nodose-petrosal-jugular ganglionic complex (NPJc), and we successfully localized the channels in the regions and the ganglia. We also investigated whether activation of the channels by agonists can trigger swallowing reflex. We also checked whether antagonist for TRPA1 and TRPV4 can reduce the agonist-induced swallowing reflexes. We also checked whether application of cold stimuli activate TRPA1 and whether it had any effect on triggering swallowing reflex. Additionally, we investigated whether TRPA1 act as mechanosensor to trigger swallowing reflex. We have already published the data in two peer-reviewed international journals. Now we are investigating the involvement of TRPV4 in water-induced swallowing reflex.
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| 今後の研究の推進方策 |
As a future plan we will conduct various experiments to understand the following research questions:
1. Expression profiles of TRPV4 channels in the swallowing-related ganglia in water-deprived rats using immunohistochemistry and qPCR.
2. Whether TRPV4 channels involved in the water-induced swallowing reflex or not.
3. Whether antagonist of TRPV4 channels reduced the water-induced swallowing reflex or not.
4. Whether mechanical stimuli activate TRPV4 channels to trigger swallowing reflex or not.
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