Suppression of epileptic seizures by regulating astrocytic cAMP signaling

通过调节星形细胞 cAMP 信号传导抑制癫痫发作

• 批准号: 19F19411
• 负责人: 池谷 裕二
• 金额: $ 1.41万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for JSPS Fellows
• 财政年份: 2019
• 资助国家: 日本
• 起止时间: 2019-10-11 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19F19411/
• 关键词: てんかん発作; アストロサイト; cyclic AMP; てんかん; cAMP; 海馬

本研究は薬物によって誘起される急性てんかんモデル、および海馬硬化による慢性てんかんモデルの2つの動物モデルを用い、アストロサイトのcAMPシグナルによるてんかん発作への影響を調べた。急性モデルの場合、てんかん誘導薬の腹腔内投与により発作を誘導した。投与するタイミングに合わせて青色光刺激をマウスの両側海馬に送り、光刺激によるアストロサイトのcAMPの上昇は発作のレベルをどのように影響したかを調べた。光刺激を受けたマウスのほとんどは重篤な発作まで至らなかった。さらも、急性モデルの場合、発作誘導後にマウスの脳を摘出し、神経細胞活動マーカーであるcFosに対する免疫染色によって光刺激、発作、または両者によって活動した海馬の神経細胞群を割り出した。慢性てんかんモデルの場合、カイニン酸を片側海馬に投与し、海馬硬化を誘導した。3週間後に、青色光刺激でアストロサイトのcAMPレベルを海馬で上昇させ、マウスの行動変化をを観察した。結果として、光刺激を受けたマウスはてんかん発作を示した。また、同じ個体を光刺激なしの条件で行動観察した場合発作はほとんど見られていないことと、bPACを発現しないてんかんモデルマウスでは光刺激による発作が見られていないことから、発作はアストロサイトのcAMP上昇によって誘導されたと考えられる。その後、マウスの脳を摘出し、海馬硬化の程度と海馬硬化による組織学的変化を免疫染色法によって確認した。本研究は今まで検討されていないアストロサイトのcAMPとてんかん発作の関係を初めて検証した。結果として、慢性てんかんモデルでは発作を抑制し、急性てんかんモデルでは発作を誘導することが明らかになった。これらの発見は、今までのてんかん発作の研究では注目されていなかったアストロサイトのcAMPシグナルが、てんかん発作の程度と有無を左右する重要な因子であることを示した。

The purpose of this study is to investigate the effects of acute and chronic sea sclerosis on the development of acute and chronic diseases. In this study, the effects of acute and chronic sea sclerosis were studied in this study. in this study, the effects of acute and chronic sea sclerosis were studied in this study. in this study, the effects of acute and chronic sea sclerosis on animals were studied in this study. The patients were given intraperitoneal injection in the abdominal cavity to guide the treatment of acute respiratory failure. In combination with the cyan light stimulation, the sea is sent, and the light stimulation is displayed on the cAMP. The light stimulation was caused by the light stimulation. The mice were killed, the mice were killed, the animals were harvested, the cells were activated, the cFos cells were stained, the cells were stimulated by light, the animals were killed, the animals were killed, and the cells of the sea were cut out. The chronic disease is caused by the combination of acid and acid tablets, and the hardening of sea fish. 3 in the morning, the cyan light stimulates the air, the cAMP, the sea, the sea and the sea. Results the results showed that the light stimulation was affected by the light stimulation and the light stimulation. In the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same way, the same body light stimulation is used to monitor the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the conditions. in the same body, the same body light stimulation is used to monitor the operation of the conditions. in the same body, the same body light stimulation is used to monitor the operation conditions, and the bPAC After treatment, the chemical immunostaining method was used to confirm the degree of sclerosis and the degree of sclerosing. The purpose of this study is to make a preliminary study of the relationship between cAMP and clinical practice. Results the results showed that the symptoms of chronic and chronic diseases were used as suppressants, and those of acute symptoms were used as guides. Today, we should pay attention to the fact that we should pay attention to the study. We should pay attention to the fact that there is a difference in the degree of cAMP and important factors.