2022 Fiscal Year Final Research Report
Efficacy of temperature-sensitive TRPM8 channels in refractory epilepsy and the elucidation of pathogenetic regulation
| Project/Area Number |
21K15269
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 47040:Pharmacology-related
|
|---|
| Research Institution | Yamaguchi University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2021-04-01 – 2023-03-31
|
| Keywords | てんかん / 脳波 / TRPM8KO / TRPM8作動薬 / 細胞外グルタミン酸 / てんかん発作 / てんかん性異常脳波 / マウス |
|---|
| Outline of Final Research Achievements |
We hypothesized that drug-induced activation of a temperature-sensitive Transient Receptor Potential Melastatin 8 (TRPM8) channel would suppress epileptic seizures in mice and conducted this study. The results showed that TRPM8 channel activators suppressed drug-induced epileptic seizures in wild type mice. In contrast, TRPM8 channel activators did not affect drug-induced epileptic seizures in TRPM8 deficient mice. In addition, we compared the epileptic seizures in TRPM8 deficient mice with wild type mice. TRPM8 deficient resulted in a shorter firing latency of epileptic discharges, and epileptic seizures to worsen. The cause was an increase in the extracellular concentration of glutamate which is one of the responsible for epileptic seizures.
|
| Free Research Field |
薬理
|
| Academic Significance and Societal Importance of the Research Achievements |
TRPM8チャネルの活性剤がてんかん治療薬の候補であることがわかった．既存の抗てんかん薬と異なる作用機序の解明ができたため薬剤抵抗性を示す難治性てんかん患者への応用が期待される．
|
