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.

癫痫是一种障碍，涉及的远远不止癫痫的发生，而且 癫痫发作可引起神经网络紊乱，导致广泛的 认知和行为障碍。到目前为止，癫痫领域的大多数工作都是 以发作事件本身的机制或预防为中心。的关注点 我的实验室一直在研究早期生命癫痫对大脑发育的影响 癫痫的发生。目前的提案扩大了我们的工作，以确定这些 机制也会引起可能导致认知功能障碍表现的改变。 在早期生活中，比如自闭症。有临床证据表明，早期生命癫痫可能是 在自闭症的许多先例中，癫痫在自闭症患者中很常见， 暗示了这两个过程之间的相互作用。我们以前和最近的工作 这表明至少在未成熟的大脑中，基线突触可塑性是 增强的癫痫发作似乎直接激活了特定的可塑性相关信号 小路。我们假设癫痫引起的可塑性障碍可能遮盖了正常 可塑性参与认知，并导致突触发育的异常模式 类似于在自闭症和其他形式的神经发育迟缓中观察到的。vbl.使用 电生理学技术，我们将首先检测癫痫诱发的时间进程 未成熟大脑中正常突触可塑性的中断。然后我们将确定 已知的特定活动依赖信号异常是否与 自闭症是在未成熟的大脑癫痫发作后重新发生的。接下来，我们将确定 癫痫的诱发机制及癫痫发作后的检测 干预减弱了神经元网络结构和功能的改变。最后， 我们将确定类似的信号、调节和突触变化 癫痫发作后和自闭症患者的人体组织中也可以观察到蛋白质。 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