STIM1-dependent calcium signaling in neuronal responses to hypoxia and ischemia
STIM1 依赖性钙信号传导在神经元对缺氧和缺血反应中的作用
基本信息
- 批准号:9036161
- 负责人:
- 金额:$ 23.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-15 至 2017-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAtaxiaBiochemicalBrainBrain Hypoxia-IschemiaBrain regionCalciumCalcium SignalingCardiopulmonary ResuscitationCause of DeathCell DeathCell physiologyCellsCerebellar DiseasesCerebellumCessation of lifeDependenceEventFoundationsFunctional disorderGoalsHeart ArrestHippocampus (Brain)HomeostasisHypoxiaImageImpaired cognitionImpairmentIn VitroInjuryIschemiaKnock-outLightMediatingMediator of activation proteinModelingMotorMusMutant Strains MiceNeurologicNeurologic DysfunctionsNeuronal InjuryNeuronsOxygenPhysiologicalPropertyPurkinje CellsRoleSignal PathwaySignal TransductionSliceStrokeSynapsesTemperatureTestingTherapeutic InterventionWorkbasebehavioral studycell injurydeprivationdisabilityhuman STIM1 proteinin vivoinhibitor/antagonistmotor disordermotor impairmentmutantnatural hypothermianeuroprotectionnovelpublic health relevancerelating to nervous systemresponse
项目摘要
DESCRIPTION (provided by applicant): Cardiac arrest and stroke are major causes of death and disability and often result in neurological impairment. Neural damage is often heterogeneous as some regions of the brain are more vulnerable to the hypoxia and ischemia (H-I) caused by these insults. The cerebellum is such a region and hypoxic and ischemic events in the cerebellum often result in ataxia and other problems with motor coordination. Neuronal calcium (Ca2+) dysregulation and Ca2+ overload are recognized as causes of cell death following brain H-I. Recently we identified stromal interaction molecules (STIM) as key components of Ca2+ signaling in excitable cells where they activate refilling of Ca2+ stores during repetitive electrical activity. Given an exceptionally high level of STIM1 expression in cerebellar Purkinje neurons and the selective vulnerability of these neurons to damage by H-I, we hypothesize that STIM1 is essential to refill Ca2+ stores and sustain Ca2+ signaling in Purkinje neurons during periods of intense synaptic activity, as occurs with H-I injury; thus, STIM1-SOCE is a critical mediator of the excitotoxic Ca2+ dysregulation and overload that causes Purkinje neuron injury and death. Our goal is to test this hypothesis by determining the fundamental properties and functions of STIM1-SOCE in Purkinje neurons during physiological and H-I conditions. For this purpose, we will carry out Ca2+ imaging, electrophysiological, morphological, and biochemical studies of cerebellar properties and function, with a focus on Purkinje neurons, in acute brain slices (Aims 1 and 2) and Purkinje neurons and other vulnerable neurons in vivo (Aim 3) in WT and STIM1 mutant mice to address the following specific aims: 1) Determine the fundamental properties and physiological functions of STIM1-dependent SOCE in cerebellar Purkinje cells, 2) Determine the contribution of STIM1-SOCE to H-I induced injury and death of Purkinje neurons in vitro, and 3) Determine the contribution of STIM1 to the neuronal damage and motor and cognitive dysfunction produced by global ischemia in vivo. These studies will begin to elucidate the role of STIM1-SOCE in Purkinje cell Ca2+ homeostasis and cerebellar function under normal physiological conditions and the contribution of STIM1-SOCE to Ca2+ overload, neuronal death, and neurological dysfunction that is produced by hypoxia and ischemia in the cerebellum and other brain regions.
描述(由申请人提供):心脏骤停和中风是死亡和残疾的主要原因,通常会导致神经功能障碍。神经损伤通常是异质的,因为大脑的某些区域更容易受到这些损伤引起的缺氧和缺血(H-I)的影响。小脑就是这样一个区域,小脑中的缺氧和缺血事件经常导致共济失调和其他运动协调问题。神经元钙(Ca ~(2+))失调和Ca ~(2+)超载被认为是脑缺血后细胞死亡的原因。最近,我们确定了基质相互作用分子(STIM)作为可兴奋细胞中Ca 2+信号传导的关键成分,在重复电活动期间,它们激活Ca 2+储存的再填充。鉴于小脑浦肯野神经元中STIM 1表达水平异常高,以及这些神经元对H-I损伤的选择性脆弱性,我们假设STIM 1对于在强烈突触活动期间重新填充浦肯野神经元中的Ca 2+储存和维持Ca 2+信号传导是必不可少的,如H-I损伤所发生的;因此,STIM 1-SOCE是引起浦肯野神经元损伤和死亡的兴奋毒性Ca 2+失调和过载的关键介质。我们的目标是通过确定生理和H-I条件下浦肯野神经元中STIM 1-SOCE的基本性质和功能来验证这一假设。为此,我们将在急性脑切片中进行小脑特性和功能的钙离子成像、电生理、形态学和生物化学研究,重点是浦肯野神经元(目的1和2)和浦肯野神经元和其他脆弱神经元(目的3)在WT和STIM 1突变小鼠体内的研究,以解决以下具体目标:1)确定小脑浦肯野细胞中STIM 1依赖性SOCE的基本性质和生理功能,2)确定STIM 1-SOCE对体外H-I诱导的浦肯野神经元损伤和死亡的贡献,和3)确定STIM 1在体内对由全脑缺血产生的神经元损伤以及运动和认知功能障碍的贡献。这些研究将开始阐明STIM 1-SOCE在正常生理条件下浦肯野细胞Ca 2+稳态和小脑功能中的作用,以及STIM 1-SOCE对小脑和其他脑区缺氧和缺血引起的Ca 2+过载、神经元死亡和神经功能障碍的贡献。
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 }}
PAUL B ROSENBERG其他文献
PAUL B ROSENBERG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('PAUL B ROSENBERG', 18)}}的其他基金
STIM1-dependent calcium signaling in neuronal responses to hypoxia and ischemia
STIM1 依赖性钙信号传导在神经元对缺氧和缺血反应中的作用
- 批准号:
9137732 - 财政年份:2015
- 资助金额:
$ 23.85万 - 项目类别:
Actigraphic assessment of sleep quality in the A4 trial
A4 试验中睡眠质量的活动记录评估
- 批准号:
8871221 - 财政年份:2015
- 资助金额:
$ 23.85万 - 项目类别:
Actigraphic assessment of sleep quality in the A4 trial
A4 试验中睡眠质量的活动记录评估
- 批准号:
9108796 - 财政年份:2015
- 资助金额:
$ 23.85万 - 项目类别:
DIADS-3: An RCT of venlafaxine for depression in AD
DIADS-3:文拉法辛治疗 AD 抑郁症的随机对照试验
- 批准号:
8237716 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
DIADS-3: An RCT of venlafaxine for depression in AD
DIADS-3:文拉法辛治疗 AD 抑郁症的随机对照试验
- 批准号:
8337846 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
DIADS-3: An RCT of venlafaxine for depression in AD
DIADS-3:文拉法辛治疗 AD 抑郁症的随机对照试验
- 批准号:
8530135 - 财政年份:2011
- 资助金额:
$ 23.85万 - 项目类别:
A Theoretically Based Memory Training Intervention in Mild Cognitive Impairment
基于理论的记忆训练干预轻度认知障碍
- 批准号:
8292063 - 财政年份:2010
- 资助金额:
$ 23.85万 - 项目类别:
The role of STIM1 in cardiac and skeletal muscle function
STIM1 在心脏和骨骼肌功能中的作用
- 批准号:
8496095 - 财政年份:2009
- 资助金额:
$ 23.85万 - 项目类别:
The role of STIM1 in cardiac and skeletal muscle function
STIM1 在心脏和骨骼肌功能中的作用
- 批准号:
8733230 - 财政年份:2009
- 资助金额:
$ 23.85万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 23.85万 - 项目类别:
Research Grant