Inflammatory regulation of neurotrophin signaling in epileptogenesis

癫痫发生中神经营养蛋白信号传导的炎症调节

基本信息

  • 批准号:
    10303038
  • 负责人:
  • 金额:
    $ 33.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-08-03 至 2023-11-30
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Epilepsy is a common neurological disorder that afflicts about 1% of the population. Although seizures can be partially controlled by current medications, there is no US FDA-approved drug that can provide disease prevention or modification despite remarkable advances in epilepsy treatment over the past decades. A major obstacle to finding such an antiepileptogenic drug is that the molecular mechanisms by which a normal brain is transformed to generate epileptic seizures remain unsolved. Accumulating evidence from recent clinical and preclinical studies suggests that the abnormal activation of the brain-derived neurotrophic factor (BDNF) receptor TrkB (tropomyosin-related kinase receptor B) and its downstream effector phospholipase Cγ1 (PLCγ1) is sufficient to produce epilepsy following status epilepticus (SE). As TrkB and PLCγ1 are emerging as attractive molecular targets to prevent acquired epilepsy, a key unsolved puzzle is the signaling events that are triggered by SE and cause the irregular BDNF/TrkA activity in the hippocampus, thereby leading to epileptogenesis. In preliminary studies we have demonstrated that the seizure-induced hippocampal BDNF/TrkB abnormality is largely suppressed by blocking prostaglandin E2 (PGE2) synthesis or signaling. Our main hypothesis is that PGE2 via a Gαs-dependent signaling pathway upregulates hippocampal BDNF/TrkB activity and contributes to epileptogenesis following prolonged seizures. Our general approach is to use biochemical, pharmacological, genetic tools, and multiple in vitro and in vivo model systems to test a hypothesis that PGE2 is involved in the hippocampal BDNF induction and TrkB activation after SE, to determine whether seizure-mediated BDNF/TrkB activity involves cAMP/PKA signaling and which Gαs-coupled PGE2 receptor is engaged, and to determine whether PGE2 signaling via its Gαs-coupled receptors plays a dominant role in the development of epilepsy and/or the associated behavioral comorbidities after SE. Successful completion of this project might lead to the discovery of novel molecular targets for the prevention strategies of acquired epilepsy.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)

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Jianxiong Jiang其他文献

Jianxiong Jiang的其他文献

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{{ truncateString('Jianxiong Jiang', 18)}}的其他基金

EP2 Antagonists for Ischemic Stroke
EP2 拮抗剂治疗缺血性中风
  • 批准号:
    10723017
  • 财政年份:
    2023
  • 资助金额:
    $ 33.25万
  • 项目类别:
Targeting TRPC3 Channels for Epileptic Seizures
针对癫痫发作的 TRPC3 通道
  • 批准号:
    10531252
  • 财政年份:
    2021
  • 资助金额:
    $ 33.25万
  • 项目类别:
Targeting TRPC3 Channels for Epileptic Seizures
针对癫痫发作的 TRPC3 通道
  • 批准号:
    10353604
  • 财政年份:
    2021
  • 资助金额:
    $ 33.25万
  • 项目类别:
Inflammatory regulation of neurotrophin signaling in epileptogenesis
癫痫发生中神经营养蛋白信号传导的炎症调节
  • 批准号:
    10058296
  • 财政年份:
    2018
  • 资助金额:
    $ 33.25万
  • 项目类别:
Prostaglandin signaling following seizures
癫痫发作后的前列腺素信号传导
  • 批准号:
    9755011
  • 财政年份:
    2018
  • 资助金额:
    $ 33.25万
  • 项目类别:
Prostaglandin signaling following seizures
癫痫发作后的前列腺素信号传导
  • 批准号:
    9077177
  • 财政年份:
    2015
  • 资助金额:
    $ 33.25万
  • 项目类别:
Prostaglandin signaling following seizures
癫痫发作后的前列腺素信号传导
  • 批准号:
    9281093
  • 财政年份:
    2015
  • 资助金额:
    $ 33.25万
  • 项目类别:
Prostaglandin signaling following seizures
癫痫发作后的前列腺素信号传导
  • 批准号:
    8487015
  • 财政年份:
    2013
  • 资助金额:
    $ 33.25万
  • 项目类别:
Prostaglandin signaling following seizures
癫痫发作后的前列腺素信号传导
  • 批准号:
    8633064
  • 财政年份:
    2013
  • 资助金额:
    $ 33.25万
  • 项目类别:

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