2020 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 |
In this project our main objective is to explore the contributions of TRPA1 and TRPV4 channels in triggering of the swallowing reflex. So far we observed TRPA1 expression mainly on thin nerve fibers and fibroblast-like cells in the sub-epithelial connective tissue layers of 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.
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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 observed that a chemical agonist for TRPA1 can trigger swallowing reflex in a dose-dependent manner up to a certain concentration. We also checked whether antagonist for TRPA1 can reduce the agonist-induced swallowing reflexes. We observed that a TRPA1 antagonist significantly reduced the number of AITC-induced swallowing reflexes.
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| Strategy for Future Research Activity |
As a future plan we will conduct various experiments to understand the following research topics:
1. Whether cold stimuli activate TRPA1 channels present in the swallowing-related regions to trigger swallowing reflex or not.
2. Whether mechanical stimuli activate TRPA1 channels present in the swallowing-related regions to trigger swallowing reflex or not.
3. Expression profiles of TRPV4 channels in the swallowing-related regions and ganglia.
4. Whether TRPV4 is functional to trigger swallowing reflex.
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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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