Donepezil increases resistance to induced seizures in a mouse model of Dravet syndrome.
Donepezil increases resistance to induced seizures in a mouse model of Dravet syndrome.
复制标题
多奈哌齐可增加 Dravet 综合征小鼠模型对诱发癫痫发作的抵抗力。
DOI：
10.1002/acn3.50848
复制
发表时间：
2019
影响因子：
5.3
通讯作者：
Escayg,Andrew
中科院分区：
文献类型：
--
作者：
Wong,JenniferC;Thelin,JacquelynT;Escayg,Andrew
SCN 1A中的新生功能丧失突变是Dravet综合征的主要原因，Dravet综合征是一种灾难性脑病，其特征为复发性早期热性惊厥、许多其他通常难以治疗的无热性惊厥类型以及行为异常，包括社交缺陷、运动功能障碍和认知障碍。我们先前证实可逆性乙酰胆碱酯酶抑制剂石杉碱甲可增加Scn 1突变体的癫痫发作抵抗力。在本研究中，我们评估了多奈哌齐（一种经美国食品药品监督管理局批准的可逆性乙酰胆碱酯酶抑制剂）在Dravet综合征（Scn 1a +/−）小鼠模型中的治疗潜力。我们发现多奈哌齐对Scn 1a +/−突变体诱导的癫痫发作具有强大的保护作用。
De novo loss‐of‐function mutations inSCN1Aare the main cause of Dravet syndrome, a catastrophic encephalopathy characterized by recurrent early‐life febrile seizures, a number of other afebrile seizure types that are often refractory to treatment, and behavioral abnormalities including social deficits, motor dysfunction, and cognitive impairment. We previously demonstrated that the reversible acetylcholinesterase inhibitor, Huperzine A, increases seizure resistance inScn1amutants. In the present study, we evaluated the therapeutic potential of donepezil, a reversible acetylcholinesterase inhibitor approved by the Food and Drug Administration, in a mouse model of Dravet syndrome (Scn1a+/−). We found that donepezil conferred robust protection against induced seizures inScn1a+/−mutants.