Selective Neuronal Knockout of STAT3 Function Inhibits Epilepsy Progression, Improves Cognition, and Restores Dysregulated Gene Networks in a Temporal Lobe Epilepsy Model

癫痫 神经科学 癫痫发生 海马结构 颞叶 生物 海马体 医学 心理学
作者
Allison E. Tipton,Yasmin Cruz Del Angel,Kathryn Hixson,Jessica Carlsen,Dana Strode,Nicolas Busquet,Michael H. Mesches,Marco I. González,Eleonora Napoli,Shelley J. Russek,Amy R. Brooks‐Kayal
出处
期刊:Annals of Neurology [Wiley]
卷期号:94 (1): 106-122 被引量:8
标识
DOI:10.1002/ana.26644
摘要

Temporal lobe epilepsy (TLE) is a progressive disorder mediated by pathological changes in molecular cascades and hippocampal neural circuit remodeling that results in spontaneous seizures and cognitive dysfunction. Targeting these cascades may provide disease-modifying treatments for TLE patients. Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) inhibitors have emerged as potential disease-modifying therapies; a more detailed understanding of JAK/STAT participation in epileptogenic responses is required, however, to increase the therapeutic efficacy and reduce adverse effects associated with global inhibition.We developed a mouse line in which tamoxifen treatment conditionally abolishes STAT3 signaling from forebrain excitatory neurons (nSTAT3KO). Seizure frequency (continuous in vivo electroencephalography) and memory (contextual fear conditioning and motor learning) were analyzed in wild-type and nSTAT3KO mice after intrahippocampal kainate (IHKA) injection as a model of TLE. Hippocampal RNA was obtained 24 h after IHKA and subjected to deep sequencing.Selective STAT3 knock-out in excitatory neurons reduced seizure progression and hippocampal memory deficits without reducing the extent of cell death or mossy fiber sprouting induced by IHKA injection. Gene expression was rescued in major networks associated with response to brain injury, neuronal plasticity, and learning and memory. We also provide the first evidence that neuronal STAT3 may directly influence brain inflammation.Inhibiting neuronal STAT3 signaling improved outcomes in an animal model of TLE, prevented progression of seizures and cognitive co-morbidities while rescuing pathogenic changes in gene expression of major networks associated with epileptogenesis. Specifically targeting neuronal STAT3 may be an effective disease-modifying strategy for TLE. ANN NEUROL 2023;94:106-122.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
么么哒荼蘼酱完成签到,获得积分10
刚刚
刚刚
小萌完成签到 ,获得积分10
刚刚
芷莯发布了新的文献求助10
1秒前
1秒前
韩涵发布了新的文献求助10
1秒前
1秒前
1秒前
2秒前
lab完成签到 ,获得积分0
2秒前
深海大菠萝完成签到,获得积分10
3秒前
啦啦啦完成签到,获得积分20
3秒前
清风与你发布了新的文献求助10
3秒前
忆前尘完成签到,获得积分10
4秒前
4秒前
烂漫的筮发布了新的文献求助10
4秒前
weiweiwei发布了新的文献求助10
4秒前
852应助tulip采纳,获得10
4秒前
研友_nVqwxL发布了新的文献求助10
5秒前
量子星尘发布了新的文献求助10
6秒前
英勇珊珊发布了新的文献求助10
7秒前
852应助小小K采纳,获得10
7秒前
7秒前
8秒前
研研发布了新的文献求助10
9秒前
9秒前
12秒前
杨佳晨发布了新的文献求助10
12秒前
酱子完成签到,获得积分10
13秒前
暴躁的阁完成签到,获得积分10
13秒前
生动茹妖完成签到,获得积分10
13秒前
尔东完成签到,获得积分10
13秒前
14秒前
敏感的伟祺完成签到,获得积分10
15秒前
Bucky完成签到,获得积分10
15秒前
烟花应助zuo采纳,获得10
16秒前
16秒前
在水一方应助178181采纳,获得200
17秒前
17秒前
猪猪hero应助一口蛋黄苏采纳,获得10
17秒前
高分求助中
Picture Books with Same-sex Parented Families: Unintentional Censorship 1000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 310
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3979289
求助须知:如何正确求助?哪些是违规求助? 3523220
关于积分的说明 11216715
捐赠科研通 3260668
什么是DOI,文献DOI怎么找? 1800176
邀请新用户注册赠送积分活动 878854
科研通“疑难数据库(出版商)”最低求助积分说明 807111