2022 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 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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| 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 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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| 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 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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| Causes of Carryover |
Need to buy antagonists and antibodies.
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