The involvement of neural stem cells in promoting elimination of pain-fear memory by lamotrigine

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07390
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Koyama Natsu 滋賀医科大学, 医学部, 准教授 (50135464)
• Co-Investigator(Kenkyū-buntansha): 中西 美保 滋賀医科大学, 医学部, 助教 (40382048)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: ラモトリギン / 恐怖回避モデル / 神経幹細胞 / ニューロスフェア / Brdu / 恐怖記憶の消去

Outline of Final Research Achievements

The effects of lamotrigine, an anticonvulsant drug with mood stabilizing effect, on the self-renewability of neural stem cell and on the fear memory were analyzed. In vitro analysis of self-renewability by neurosphere assay of the periventricular region showed increased proliferation of cell masses in a lamotrigine dose-dependent manner. In vivo analysis by the BrdU method also showed that administration of lamotrigine for 12 weeks amplified the progenitor pool producing new neurons in the subependymal zone: SEZ and subgranular zone: SGZ of the hippocampal dentate gyrus. In the fear conditioning test, fear responsiveness during associative learning was enhanced, but no enhancement of fear memory was observed. These results suggest that the enhancement of self-renewability of neural stem cell by lamotrigine may prevent excessive fear response.

Free Research Field

神経生理学

Academic Significance and Societal Importance of the Research Achievements

慢性痛を訴える成人は、意外なことに働き盛りの世代で最も多く、慢性痛による経済的損失を減少させるために、慢性痛のメカニズムを解明する研究は重要である。「恐怖回避モデル」が背景にある慢性の痛みに対しては、痛みに対する過剰な恐怖記憶の鎮静化が治療において重要となると考えられる。気分安定薬作用のあるラモトリギンによる、神経幹細胞の事項複製能の促進作用と恐怖記憶の鎮静化作用が確認されれば、副作用の出ない用量でのラモトリギンの投与は、難治性の慢性痛に対して行われる運動療法と心理療法の効果を促進させる可能性が予想される。