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，涉及远远超过癫痫发作， 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 集中于发作事件本身的机制或预防。的焦点 我的实验室一直在研究早期癫痫发作对大脑发育的影响， 癫痫发生目前的建议扩大了我们的工作，以确定这些是否 这些机制也会引起可能导致认知功能障碍的改变， 比如自闭症有临床证据表明，生命早期癫痫发作可能是一个 自闭症的许多先例中，癫痫在自闭症患者中很常见， 这表明这两个过程之间存在相互作用。我们以前和最近的工作 这表明，至少在未成熟的大脑中， 增强的癫痫发作似乎直接激活了特定的可塑性相关信号 途径。我们假设癫痫引起的“发育不良”可能会阻塞正常的 可塑性参与认知，并诱导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情况。使用 电生理技术，我们将首先检查的时间过程中， 未成熟大脑正常突触可塑性的中断。然后我们将决定 是否已知特定的活性依赖性信号传导异常与 自闭症是在未成熟的大脑中癫痫发作后重新出现的。接下来，我们将确定 癫痫发作诱导的机制，他们的激活和测试是否癫痫发作后 干预减弱了神经元网络的改变的结构和功能。最后， 我们将确定是否在信号传导、调节和突触 在癫痫发作和自闭症患者的人体组织中也观察到了这种蛋白质 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