Understanding the Cognitive Impact of Early Life Epilepsy

了解早期癫痫对认知的影响

• 批准号: 8650480
• 负责人: Frances E Jensen
• 金额: $ 23.84万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8650480
• 关键词: Understanding; Cognitive; Impact; Early; Life

Epilepsy is a disorder that involves far more than the occurrence of seizures, and seizures can cause neuronal network disturbances that result in a wide range of cognitive and behavioral impairment. To date, most work in the epilepsy field has centered on the mechanism or prevention of the ictal events themselves. The focus of my laboratory has been on the impact of early life seizures on brain development and epileptogenesis. The present proposal extends our work to determine whether these mechanisms also induce alterations that could lead to cognitive dysfunction manifesting in early life, such as autism. There is clinical evidence that early life seizures may be one of many precedents for autism, and epilepsy is common in patients with autism, suggesting an interaction between the two processes. Our prior and recent work suggests that at least in the immature brain, where baseline synaptic plasticity is enhanced, seizures appear to directly activate specific plasticity-associated signaling pathways. We hypothesize that seizure induced ¿dysplasticity¿ may occlude normal plasticity involved in cognition, and induce abnormal patterns of synapse development similar to those observed in autism and other forms of neurodevelopmental delay. Using electrophysiological techniques, we will first examine the time course of seizure-induced interruption of normal synaptic plasticity in the immature brain. We will then determine whether specific activity-dependent signaling abnormalities known to be associated with autism occur de novo following seizures in the immature brain. Next, we will identify seizure induced mechanisms for their activation and test whether post-seizure intervention attenuates the altered structure and function of neuronal networks. Finally, we will determine whether similar alterations in signaling, regulatory, and synaptic proteins also are observed in human tissue following seizures and in cases of autism associated with neonatal or infantile seizures.

癫痫是一种疾病，涉及癫痫发作的发生远远超过 癫痫发作会导致神经元网络灾难，导致广泛 认知和行为障碍。迄今为止，癫痫领域的大多数工作 集中于发作事件本身的机制或预防。重点 我的实验室一直对早期癫痫发作对大脑发育的影响和 癫痫发生。本提案扩展了我们的工作，以确定这些建议是否 机制还会影响可能导致认知功能障碍表现的变化 在早期生活中，例如自闭症。有临床证据表明早期癫痫发作可能是一个 自闭症的许多先例，癫痫病在自闭症患者中很常见 暗示两个过程之间的相互作用。我们的先前和最近工作 表明至少在未成熟的大脑中，基线合成可塑性为 增强的癫痫发作似乎直接激活了与可塑性相关的特定信号传导 途径。我们假设癫痫发作引起的e塑性性可能会阻塞正常 认知涉及的可塑性，并诱导突触发展的异常模式 与自闭症和其他形式的神经发育延迟中观察到的类似。使用 电生理技术，我们将首先检查癫痫发作的时间过程 未成熟大脑中正常突触可塑性的中断。然后我们将确定 特定的活动依赖性信号传导异常是否已知与 自闭症发生在未成熟大脑中的癫痫发作后。接下来，我们将确定 癫痫发作的激活机制并测试塞兹后是否是否 干预减轻了神经元网络的结构和功能的改变。最后， 我们将确定信号，调节和突触的类似变化是否 在癫痫发作后，在人体组织中也观察到蛋白质，并且在自闭症的情况下 与新生儿或婴儿癫痫发作有关。

项目成果

Altered hippocampal dendritic spine maturation after hypoxia-induced seizures in neonatal rats.

新生大鼠缺氧诱发癫痫发作后海马树突棘成熟发生改变。

• DOI: 10.1016/j.mcn.2021.103629
• 发表时间: 2021
• 期刊: Molecular and cellular neurosciences
• 作者: Lippman-Bell,JocelynJ;Handy,Marcus;Nieder,CassidyG;Getzfread,Mollie;Jensen,FrancesE
• 通讯作者: Jensen,FrancesE

Benign rolandic epileptiform discharges are associated with mood and behavior problems.

• DOI: 10.1016/j.yebeh.2011.06.023
• 发表时间: 2011-10
• 期刊: Epilepsy & behavior : E&B
• 作者: Sarco DP;Boyer K;Lundy-Krigbaum SM;Takeoka M;Jensen F;Gregas M;Waber DP
• 通讯作者: Waber DP