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2022 年度 実施状況報告書

Elucidating Novel Therapeutic Targets for Oropharyngeal Dysphagia: Focusing on TRPA1 and TRPV4 Channels

研究課題

研究課題/領域番号 20K09898
研究機関松本歯科大学

研究代表者

Hossain M.Zakir  松本歯科大学, 歯学部, 講師 (40792445)

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)
研究期間 (年度) 2020-04-01 – 2024-03-31
キーワードSwallowing Reflex / TRPA1 / TRPV4
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.

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.

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.

次年度使用額が生じた理由

Need to buy antagonists and antibodies.

  • 研究成果

    (3件)

すべて 2023 2022

すべて 雑誌論文 (2件) (うち査読あり 2件、 オープンアクセス 2件) 学会発表 (1件)

  • [雑誌論文] Pharmacological activation of transient receptor potential vanilloid 4 promotes triggering of the swallowing reflex in rats2023

    • 著者名/発表者名
      Hossain Mohammad Zakir、Ando Hiroshi、Unno Shumpei、Roy Rita Rani、Kitagawa Junichi
    • 雑誌名

      Frontiers in Cellular Neuroscience

      巻: 17 ページ: -

    • DOI

      10.3389/fncel.2023.1149793

    • 査読あり / オープンアクセス
  • [雑誌論文] TRPA1s act as chemosensors but not as cold sensors or mechanosensors to trigger the swallowing reflex in rats2022

    • 著者名/発表者名
      Hossain Mohammad Zakir、Ando Hiroshi、Unno Shumpei、Kitagawa Junichi
    • 雑誌名

      Scientific Reports

      巻: 12 ページ: 3431

    • DOI

      10.1038/s41598-022-07400-3

    • 査読あり / オープンアクセス
  • [学会発表] Involvement of TRPV4 channels expressed in the afferents of superior laryngeal nerve for triggering swallowing reflex2022

    • 著者名/発表者名
      安藤 宏、Mohammad Zakir Hossain、Rita Rani Roy、海野 俊平、北川 純一
    • 学会等名
      日本味と匂学会 第56回大会

URL: 

公開日: 2023-12-25  

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