Optogenetic hub cell control for no seizures, no side-effects in temporal lobe ep
光遗传学枢纽细胞控制无癫痫发作,颞叶 ep 无副作用
基本信息
- 批准号:8624720
- 负责人:
- 金额:$ 28.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2015-07-21
- 项目状态:已结题
- 来源:
- 关键词:AdultAdverse effectsAffectAnimal ModelAnimalsAntiepileptic AgentsBrainCellsChronicComputer SimulationDataDoseDrug resistanceEpilepsyEventFrequenciesGenerationsGoalsHippocampus (Brain)HumanIn VitroLasersLearningLightLimbic SystemMaintenanceMedialMedicalMemoryMethodsModelingMusNational Institute of Neurological Disorders and StrokeNeuronsOpticsPathway interactionsPatientsPharmaceutical PreparationsPharmacotherapyPlayPopulationRattusRecurrenceResearchRoleSeizuresSliceSpecificitySynapsesTechniquesTemporal LobeTemporal Lobe EpilepsyTestingTherapeuticTimedentate gyrusentorhinal cortexgranule cellin vivoinformation processingkainatenovelnovel strategiesnovel therapeutic interventionoptogeneticspreventresearch studysocialtherapy resistant
项目摘要
DESCRIPTION (provided by applicant): Temporal lobe epilepsy is the most common form of epilepsy in adults. Currently available anti-epileptic drugs often have significant and debilitating side-effects, and temporal lobe epilepsy frequently becomes resistant to drug therapy, presenting an enormous social and medical problem. The central idea behind the proposed research is that it may be possible to achieve seizure control by transiently inhibiting, only at critical moments, the activity of a low number of unique neurons that may be primarily responsible to triggering seizures in the limbic system. Our recent large-scale computational modeling studies have shown that rare, abnormal, super- connected, hub-like neurons may play a key role in seizure initiation. Subsequently, such hub cells have been demonstrated in the healthy developing hippocampus, and it has been shown that modulation of single hub cells in slices can block the spontaneous bursting activity of the entire network. Here we propose to use novel optogenetic approaches to selectively inhibit abnormal hub-like cells in the dentate gyrus and entorhinal cortex of epileptic adult mice in vivo in order to prevent the hyper-activation of the commissural-associational and temporo-ammonic pathways within the entorhino-hippocampal network specifically at the onset of spontaneous recurrent seizures. Because the manipulation will affect only a few cells in the entire limbic system in a temporally selective manner, effective seizure control may be achieved with minimal effects on the normal information processing of the circuit. If successful, the proposed research will demonstrate a fundamentally novel approach to achieving the goal of "no seizures, no side-effects" for the treatment of epilepsy.
描述(由申请人提供):颞叶癫痫是成人最常见的癫痫形式。目前可用的抗癫痫药物通常具有显着且使人衰弱的副作用,颞叶癫痫经常对药物治疗产生耐药性,从而带来巨大的社会和医学问题。这项研究背后的中心思想是,通过仅在关键时刻短暂抑制少量独特神经元的活动,可能会实现癫痫控制,而这些神经元可能主要负责触发边缘系统中的癫痫发作。我们最近的大规模计算模型研究表明,罕见的、异常的、超连接的中枢样神经元可能在癫痫发作的发生中发挥关键作用。随后,这种中枢细胞在健康发育的海马体中得到了证实,并且已经证明,对切片中的单个中枢细胞进行调节可以阻止整个网络的自发爆发活动。在这里,我们建议使用新颖的光遗传学方法选择性抑制体内癫痫成年小鼠的齿状回和内嗅皮质中的异常轮毂样细胞,以防止内嗅海马网络内的连合-关联和颞-氨通路过度激活,特别是在自发性复发性癫痫发作时。由于操作只会以时间选择性的方式影响整个边缘系统中的少数细胞,因此可以在对电路的正常信息处理影响最小的情况下实现有效的癫痫控制。如果成功,拟议的研究将展示一种全新的方法来实现癫痫治疗“无癫痫发作、无副作用”的目标。
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(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
IVAN SOLTESZ其他文献
IVAN SOLTESZ的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('IVAN SOLTESZ', 18)}}的其他基金
2019 Inhibition in the CNS Gordon Research Conference and Gordon Research Seminar
2019年中枢神经系统戈登研究会议和戈登研究研讨会的抑制
- 批准号:
9750981 - 财政年份:2019
- 资助金额:
$ 28.77万 - 项目类别:
Full-scale biophysical modeling of hippocampal networks during spatial navigation and memory replay
空间导航和记忆回放过程中海马网络的全面生物物理建模
- 批准号:
10202755 - 财政年份:2017
- 资助金额:
$ 28.77万 - 项目类别:
Optogenetic hub cell control for no seizures, no side-effects temporal lobe epilepsy
光遗传学中心细胞控制无癫痫发作,无副作用颞叶癫痫
- 批准号:
9165938 - 财政年份:2015
- 资助金额:
$ 28.77万 - 项目类别:
Towards a Complete Description of the Circuitry Underlying Memory replay.
实现内存重放底层电路的完整描述。
- 批准号:
8935978 - 财政年份:2014
- 资助金额:
$ 28.77万 - 项目类别:
Towards a Complete Description of the Circuitry Underlying Memory replay.
实现内存重放底层电路的完整描述。
- 批准号:
9265151 - 财政年份:2014
- 资助金额:
$ 28.77万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 28.77万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 28.77万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 28.77万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 28.77万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
Downsides of downhill: The adverse effects of head vibration associated with downhill mountain biking on visuomotor and cognitive function
速降的缺点:与速降山地自行车相关的头部振动对视觉运动和认知功能的不利影响
- 批准号:
2706416 - 财政年份:2022
- 资助金额:
$ 28.77万 - 项目类别:
Studentship