2021 Fiscal Year Research-status Report
Elucidating Novel Therapeutic Targets for Oropharyngeal Dysphagia: Focusing on TRPA1 and TRPV4 Channels
| Project/Area Number |
20K09898
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
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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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Keywords | Swallowing Reflex / TRPA1 / TRPV4 |
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| Outline of Annual Research Achievements |
This project aimed to understand the contributions of TRPA1 and TRPV4 channels in triggering of the swallowing reflex. So far we obtained data for TRPA1 and published the data. TRPA1 expression observed mainly on thin nerve fibers and fibroblast-like cells in the superior laryngeal nerve (SLN)-innervated swallowing-related regions. In the nodose-petrosal-jugular ganglionic complex (NPJc), they were mainly localized on unmyelinated neurons. We also observed that topical application of a chemical agonist for TRPA1, allyl isothiocyanate (AITC), in
the swallowing-related regions dose-dependently facilitated the triggering of swallowing reflex. Prior topical application of a antagonist for TRPA1 significantly reduced the AITC-induced swallowing reflex. 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" journal. Now we are focusing on research related to TRPV4 channels.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
Our research is progressing smoothly as planned. In last fiscal year we conducted immunohistochemistry studies to understand the expression
profile of TRPA1 channels in the SLN-innervated swallowing related-regions and in the 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 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 related to TRPA1. Now we are conducting research related to TRPV4.
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| Strategy for Future Research Activity |
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 regions and ganglia using immunohistochemistry and PCR.
2. Whether agonist of TRPV4 channels trigger swallowing reflex or not.
3. Whether antagonist of TRPV4 channels reduce the number of agonist-induced swallowing reflex or not.
4. Whether mechanical stimuli activate TRPV4 channels present in the swallowing-related regions to trigger swallowing reflex or not.
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| Causes of Carryover |
Need to buy antagonists and antibodies. We plan to buy in next fiscal year and use them in research.
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