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以不同神经元群体中[基因名称]敲低作为安吉尔曼综合征模型,研究丙戊酸盐对癫痫样活动的影响。 (注:原文中“with a knockdown of in different neuronal populations”部分“”处应有具体基因名称未给出)

Effects of valproate on seizure-like activity in with a knockdown of in different neuronal populations as a model of Angelman Syndrome.

作者信息

Moore Madeline C, Taylor Danielle T

机构信息

Department of Biology, Utah Valley University, Orem, UT, USA.

出版信息

Epilepsy Behav Rep. 2023 Sep 28;24:100622. doi: 10.1016/j.ebr.2023.100622. eCollection 2023.

Abstract

Angelman Syndrome is a rare, genetically induced neurodevelopmental disorder. This disorder stems from a mutation or deletion of the maternal gene. Characteristics of this disease include developmental delay, recurring seizures, and severe intellectual disabilities. We studied seizure activity in male with a knockdown of in different neuronal populations (GABAergic, glutamatergic, mushroom body, and all neurons) and investigated the effects of the antiseizure medication (ASM) on seizure-like activity. Epileptiform activity was monitored in individual fruit flies using imaging chambers and mechanically induced seizures using a vortex assay. A positive control was also used: ( seizure phenotype). Seizure activity was analyzed for sums of seizure durations, number of seizures, and total time to return to normal activity.  knockdowns in GABAergic neurons elicited more seizure-like episodes than knockdowns in glutamatergic neurons and were on par with the positive control group and those with knockdowns in the mushroom bodies. We have established a method whereby valproate could be administered through food rather than through injections to effectively treat epileptiform activity. We demonstrated that if is not knocked down pan-neuronally, Angelman Syndrome seizure-like activity can be studied using and therefore allows for high-throughput drug discovery.

摘要

安吉尔曼综合征是一种罕见的、由基因引起的神经发育障碍。这种疾病源于母系基因的突变或缺失。该疾病的特征包括发育迟缓、反复发作的癫痫和严重的智力残疾。我们研究了在不同神经元群体(γ-氨基丁酸能、谷氨酸能、蘑菇体和所有神经元)中敲低某物质的雄性个体的癫痫活动,并研究了抗癫痫药物(ASM)对癫痫样活动的影响。使用成像室监测单个果蝇中的癫痫样活动,并使用涡旋试验机械诱导癫痫发作。还使用了阳性对照:(癫痫表型)。分析癫痫发作活动的癫痫发作持续时间总和、癫痫发作次数以及恢复正常活动的总时间。γ-氨基丁酸能神经元中的敲低比谷氨酸能神经元中的敲低引发更多癫痫样发作,并且与阳性对照组以及蘑菇体中敲低的组相当。我们建立了一种方法,通过食物而非注射来给予丙戊酸盐,以有效治疗癫痫样活动。我们证明,如果不是全神经元敲低某物质,可以使用某物质来研究安吉尔曼综合征癫痫样活动,因此可用于高通量药物发现。

需注意,原文中部分关键物质未明确写出具体名称,译文里用“某物质”代替,可能影响对完整内容的准确理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6155/10570944/4156992cccf5/gr1.jpg

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