The roles and mechanisms of GABA receptor activation in regulating neurogenesis i

GABA受体激活在调节神经发生中的作用和机制

基本信息

  • 批准号:
    8123112
  • 负责人:
  • 金额:
    $ 29.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-09-01 至 2014-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Neurogenesis was traditionally believed to occur only during embryonic development in mammals. Only recently has it become generally accepted that new neurons are indeed continuously produced and integrated in discrete regions of the adult mammalian central nervous system. Adult neurogenesis recapitulates the complete process of the neuronal development, from fate specification of neural progenitors, migration, synaptic integration and maturation of newborn dentate granule cells (DGCs). The molecular mechanisms that regulate these neurogenesis steps are largely unknown. Gamma-amino butyric acid (GABA), one of the major inhibitory neurotransmitters in the adult central nervous system, activates GABA receptors in the tonic/phasic mechanisms. Emerging evidence suggests that GABA receptor activity also plays an essential role in regulating the adult neurogenesis. The specific contribution of tonic and/or phasic GABA activation to the proliferation and differentiation of adult neural progenitors and the synaptic integration of their progeny, however, is unknown, and will be examined in our current proposal. Specific Aim I: To determine the roles of tonic GABA receptor activation in regulating proliferation and fate specification of neural progenitors in the adult brain. Specific Aim II: To examine the specific roles of tonic and/or phasic GABA receptor activation in synapse formation and maturation of newborn DGCs in the adult brain. Specific Aim III: To determine the roles of GABA receptor activation in the formation of functional synapses by the axons of newborn DGCs in the adult brain. The approach will be to use engineered retroviruses to genetically manipulate GABAergic activity of the adult neural progenitors and their progeny. The proliferation and differentiation of these genetically-manipulated adult neural progenitors and the synaptic integration of these newborn neurons will be examined. Understanding these regulatory mechanisms for adult neurogenesis may provide clues into the etiology and pathology of these brain disorders and diseases. More importantly, these studies may shed light on novel therapy development such as functional replacement of damaged neurons in degenerative neurological disease utilizing stem cells, including both embryonic stem cells and adult neural stem cells. PUBLIC HEALTH RELEVANCE: The adult brain is capable of generating new neurons throughout adulthood. These newborn neurons in the adult brain can successfully integrate into the adult brain. However, we have yet to understand how these new neurons are generated and how these neurons can make the right connections with the existing neurons in the brain. The development of these new neurons shares similar mechanisms with embryonic neuronal development, in which the neurotransmitter, gamma-amino butyric acid (GABA) plays an important role. We propose to decipher the mechanisms of GABA receptor activation in regulating adult neurogenesis. Understanding the kind of factors regulating the generation of these new neurons may provide clues into the etiology and pathology of the brain disorders and diseases. Our studies may potentially lead to the development of novel therapy such as functional replacement of damaged neurons in degenerative neurological disease utilizing stem cells, including both embryonic stem cells and adult neural stem cells.
描述(由申请人提供):传统上认为神经发生仅发生在哺乳动物的胚胎发育期间。直到最近,人们才普遍接受,新的神经元确实是不断产生和整合在成年哺乳动物中枢神经系统的离散区域。成体神经发生是神经元发育的一个完整过程,从神经祖细胞的命运特化、迁移、突触整合到新生齿状核颗粒细胞(dentate granule cells,DGCs)的成熟。调节这些神经发生步骤的分子机制在很大程度上是未知的。γ-氨基丁酸(GABA)是成年人中枢神经系统中主要的抑制性神经递质之一,在紧张/相位机制中激活GABA受体。越来越多的证据表明,GABA受体活性在调节成体神经发生中也起着至关重要的作用。然而,具体的贡献,紧张和/或阶段性GABA激活成人神经祖细胞的增殖和分化及其后代的突触整合,是未知的,将在我们目前的建议进行检查。具体目标一:目的:探讨强直性GABA受体激活在成年脑神经前体细胞增殖和命运特化中的作用。具体目标二:研究GABA受体的强直性和/或时相性激活在成年脑内新生DGC突触形成和成熟中的特定作用。具体目标三:目的:探讨GABA受体激活在成年人新生DGC轴突形成功能性突触中的作用。该方法将使用工程逆转录病毒来遗传操纵成体神经祖细胞及其后代的GABA能活性。将检查这些遗传操作的成年神经祖细胞的增殖和分化以及这些新生神经元的突触整合。了解这些成人神经发生的调节机制可能会为这些脑疾病和疾病的病因和病理提供线索。更重要的是,这些研究可能为新型疗法的开发提供线索,例如利用干细胞(包括胚胎干细胞和成人神经干细胞)功能性替代退行性神经系统疾病中受损的神经元。 公共卫生相关性:成年人的大脑能够在整个成年期产生新的神经元。这些新生的神经元在成人大脑中可以成功地整合到成人大脑中。然而,我们还没有了解这些新神经元是如何产生的,以及这些神经元如何与大脑中现有的神经元建立正确的连接。这些新神经元的发育与胚胎神经元发育具有相似的机制,其中神经递质γ-氨基丁酸(GABA)起着重要作用。我们建议破译GABA受体激活调节成人神经发生的机制。了解调节这些新神经元产生的因素可能会为大脑疾病和疾病的病因学和病理学提供线索。我们的研究可能会导致开发新的治疗方法,例如利用干细胞(包括胚胎干细胞和成体神经干细胞)功能性替代退行性神经疾病中受损的神经元。

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 }}

Shaoyu Ge其他文献

Shaoyu Ge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('Shaoyu Ge', 18)}}的其他基金

Examine the local glucose dynamics in activity-induced hippocampal neurogenesis
检查活动诱导的海马神经发生中的局部葡萄糖动态
  • 批准号:
    10572244
  • 财政年份:
    2022
  • 资助金额:
    $ 29.12万
  • 项目类别:
Mechanistic study of declining hippocampal neurogenesis in the aging brain
衰老大脑海马神经发生下降的机制研究
  • 批准号:
    10577735
  • 财政年份:
    2020
  • 资助金额:
    $ 29.12万
  • 项目类别:
Functional neurovascular coupling in a mouse model of Alzheimer's Disease
阿尔茨海默病小鼠模型中的功能性神经血管耦合
  • 批准号:
    10285083
  • 财政年份:
    2020
  • 资助金额:
    $ 29.12万
  • 项目类别:
Mechanistic study of declining hippocampal neurogenesis in the aging brain
衰老大脑海马神经发生下降的机制研究
  • 批准号:
    10334527
  • 财政年份:
    2020
  • 资助金额:
    $ 29.12万
  • 项目类别:
To explore the development and function of clonally-related adult-born dentate gr
探讨克隆相关的成年齿状细胞的发育和功能
  • 批准号:
    8772093
  • 财政年份:
    2014
  • 资助金额:
    $ 29.12万
  • 项目类别:
Viral tools for studying NG2 cells
用于研究 NG2 细胞的病毒工具
  • 批准号:
    8537790
  • 财政年份:
    2012
  • 资助金额:
    $ 29.12万
  • 项目类别:
Viral tools for studying NG2 cells
用于研究 NG2 细胞的病毒工具
  • 批准号:
    8451018
  • 财政年份:
    2012
  • 资助金额:
    $ 29.12万
  • 项目类别:
The roles and mechanisms of GABA receptor activation in regulating neurogenesis i
GABA受体激活在调节神经发生中的作用和机制
  • 批准号:
    8312561
  • 财政年份:
    2009
  • 资助金额:
    $ 29.12万
  • 项目类别:
The roles and mechanisms of GABA receptor activation in regulating neurogenesis i
GABA受体激活在调节神经发生中的作用和机制
  • 批准号:
    8531359
  • 财政年份:
    2009
  • 资助金额:
    $ 29.12万
  • 项目类别:
The roles and mechanisms of GABA receptor activation in regulating neurogenesis i
GABA受体激活在调节神经发生中的作用和机制
  • 批准号:
    7790926
  • 财政年份:
    2009
  • 资助金额:
    $ 29.12万
  • 项目类别:

相似国自然基金

层出镰刀菌氮代谢调控因子AreA 介导伏马菌素 FB1 生物合成的作用机理
  • 批准号:
    2021JJ40433
  • 批准年份:
    2021
  • 资助金额:
    0.0 万元
  • 项目类别:
    省市级项目
寄主诱导梢腐病菌AreA和CYP51基因沉默增强甘蔗抗病性机制解析
  • 批准号:
    32001603
  • 批准年份:
    2020
  • 资助金额:
    24.0 万元
  • 项目类别:
    青年科学基金项目
AREA国际经济模型的移植.改进和应用
  • 批准号:
    18870435
  • 批准年份:
    1988
  • 资助金额:
    2.0 万元
  • 项目类别:
    面上项目

相似海外基金

Onboarding Rural Area Mathematics and Physical Science Scholars
农村地区数学和物理科学学者的入职
  • 批准号:
    2322614
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
TRACK-UK: Synthesized Census and Small Area Statistics for Transport and Energy
TRACK-UK:交通和能源综合人口普查和小区域统计
  • 批准号:
    ES/Z50290X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Research Grant
Wide-area low-cost sustainable ocean temperature and velocity structure extraction using distributed fibre optic sensing within legacy seafloor cables
使用传统海底电缆中的分布式光纤传感进行广域低成本可持续海洋温度和速度结构提取
  • 批准号:
    NE/Y003365/1
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Research Grant
Point-scanning confocal with area detector
点扫描共焦与区域检测器
  • 批准号:
    534092360
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Major Research Instrumentation
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
  • 批准号:
    2326714
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
Collaborative Research: Scalable Manufacturing of Large-Area Thin Films of Metal-Organic Frameworks for Separations Applications
合作研究:用于分离应用的大面积金属有机框架薄膜的可扩展制造
  • 批准号:
    2326713
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
Unlicensed Low-Power Wide Area Networks for Location-based Services
用于基于位置的服务的免许可低功耗广域网
  • 批准号:
    24K20765
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
  • 批准号:
    2427233
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
Postdoctoral Fellowship: OPP-PRF: Tracking Long-Term Changes in Lake Area across the Arctic
博士后奖学金:OPP-PRF:追踪北极地区湖泊面积的长期变化
  • 批准号:
    2317873
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
RAPID: Collaborative Research: Multifaceted Data Collection on the Aftermath of the March 26, 2024 Francis Scott Key Bridge Collapse in the DC-Maryland-Virginia Area
RAPID:协作研究:2024 年 3 月 26 日 DC-马里兰-弗吉尼亚地区 Francis Scott Key 大桥倒塌事故后果的多方面数据收集
  • 批准号:
    2427232
  • 财政年份:
    2024
  • 资助金额:
    $ 29.12万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了