Project 1: The Reciprocal Relationship between Binge Drinking and Astrocytic Signaling
项目 1:酗酒与星形胶质细胞信号传导之间的相互关系
基本信息
- 批准号:10540965
- 负责人:
- 金额:$ 18.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-20 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAffectAlcohol consumptionAlcohol dependenceAlcoholsAnti-Inflammatory AgentsAreaAstrocytesAttenuatedBehaviorBehavioralBiological AssayBrainBrain InjuriesBrain-Derived Neurotrophic FactorCellsCognitive deficitsConsummatory BehaviorConsumptionCountryDependenceDevelopmentEnzyme-Linked Immunosorbent AssayEthanolEthanol dependenceEventFunctional disorderFutureG Protein-Coupled Receptor SignalingGLAST ProteinGlial Fibrillary Acidic ProteinGlutamate TransporterGlutamatesGrantHeavy DrinkingHippocampus (Brain)HumanImmuneImmunocompetentImmunohistochemistryIncidenceInflammatoryInterleukin-1Interleukin-1 betaInterleukin-10IntoxicationLeadLinkMeasuresMediatingMemoryMemory impairmentMicrodialysisMinorityModelingMolecularMorphologyMusNeuroimmuneNeuroimmune systemNeuroimmunomodulationNeuronal PlasticityPhenotypePlayProceduresQuantitative Reverse Transcriptase PCRReceptor SignalingRegulationReportingResearchRiskRoleSex DifferencesSignal TransductionSiteTestingUnited StatesViralWorkalcohol abuse therapyalcohol effectalcohol researchalcohol use disorderanakinrabinge drinkingcombatcytokinedesigner receptors exclusively activated by designer drugsdrinkingexperimental studyextracellularglutamatergic signalinghealth disparityhealth economicsimprovedinnovationinsightneuroinflammationneurotransmissionnovelnovel therapeuticsobject recognitionpreventresponsesexsocioeconomicssynaptic functionuptake
项目摘要
Project Abstract: Excessive binge alcohol consumption causes major health and socio-economic issues within
the United States. Unfortunately, minorities in this country are disproportionately burdened by these problems
despite equal incidences of binge drinking. Finding ways to reduce binge like consumption therefore remains an
important field of research to combat health disparities and decrease the development of ethanol dependence.
This project seeks to determine if astrocytes and the neuroimmune system represent novel targets by which to
curb excessive consumption. This grant determines the influence of excessive ethanol on astrocytic activation
and function in the hippocampus as well if the proinflammatory cytokines are responsible for glial maladaptations
(Aim 1). Because sex-differences can alter neuroimmune responses, these studies will elucidate the impact of
sex on both astrocyte activation and their function. Secondly, these studies will determine if hippocampal
astrocytic signaling can be switched to reverse the influences of ethanol on the increased proinflammatory
microenvironment and decreased glutamatergic tone of the hippocampus (Aim 2). Finally, because both
glutamate and proinflammatory cytokines can impact hippocampal dependent memory tasks and consummatory
behaviors, these experiments will determine the impact of astrocytic signaling on ethanol consumption and
alcohol-induced cognitive deficits (Aim 2). The development of astrocyte specific DREADDs allows us to
manipulate G-protein coupled receptor signaling in the hippocampus using site directed stereotactic viral
delivery. Altogether, these two aims will test our overall hypothesis that there is a reciprocal and reinforcing
relationship between alcohol and astrocyte activation mediated by the influence of astrocytes on glutamatergic
tone and proinflammatory signaling cascades. These innovative studies will provide insight into the role of
astrocytes in the transition to alcohol dependence as well as the influence of alcohol-induced neuroimmune
dysregulation on the astrocytic response.
项目摘要:过度饮酒会导致严重的健康和社会经济问题,
美国的不幸的是,这个国家的少数民族不成比例地承受着这些问题的负担
尽管酗酒的发生率相同因此,找到减少暴饮暴食的方法仍然是一个问题。
这是消除健康差距和减少乙醇依赖的重要研究领域。
该项目旨在确定星形胶质细胞和神经免疫系统是否代表新的靶点,
抑制过度消费。这项研究确定了过量乙醇对星形胶质细胞活化的影响
如果促炎细胞因子是神经胶质适应不良的原因,
(Aim 1)。由于性别差异可以改变神经免疫反应,这些研究将阐明
性别对星形胶质细胞的激活及其功能的影响。其次,这些研究将确定海马是否
星形胶质细胞信号传导可以被转换以逆转乙醇对增加的促炎性细胞因子的影响。
微环境和降低海马的神经元紧张性(Aim 2)。最后,因为两者
谷氨酸和促炎细胞因子可以影响海马依赖性记忆任务和完成性记忆任务。
行为,这些实验将确定星形胶质细胞信号对乙醇消耗的影响,
酒精诱导的认知缺陷(目标2)。星形胶质细胞特异性DREADD的发展使我们能够
使用定点立体定向病毒操纵海马中的G蛋白偶联受体信号传导
交付.总而言之,这两个目标将检验我们的总体假设,即存在一种相互强化的
酒精与星形胶质细胞活化的关系--星形胶质细胞对酒精代谢的影响
紧张和促炎信号级联。这些创新的研究将提供深入了解的作用,
星形胶质细胞向酒精依赖转化过程中的作用及酒精对神经免疫的影响
星形胶质细胞反应失调。
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)
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Simon Alexander Marshall的其他文献
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{{ truncateString('Simon Alexander Marshall', 18)}}的其他基金
Project 1: The Reciprocal Relationship between Binge Drinking and Astrocytic Signaling
项目 1:酗酒与星形胶质细胞信号传导之间的相互关系
- 批准号:
10705859 - 财政年份:2022
- 资助金额:
$ 18.65万 - 项目类别:
The Reciprocal Relationship between Binge Drinking and Astrocytic Signaling
暴饮暴食与星形胶质细胞信号传导之间的相互关系
- 批准号:
10541714 - 财政年份:2022
- 资助金额:
$ 18.65万 - 项目类别:
Scientific Mentoring and Research Experiences Core
科学指导和研究经验核心
- 批准号:
10540964 - 财政年份:2022
- 资助金额:
$ 18.65万 - 项目类别:
The Reciprocal Relationship between Binge Drinking and Astrocytic Signaling
暴饮暴食与星形胶质细胞信号传导之间的相互关系
- 批准号:
10705754 - 财政年份:2022
- 资助金额:
$ 18.65万 - 项目类别:
Scientific Mentoring and Research Experiences Core
科学指导和研究经验核心
- 批准号:
10705857 - 财政年份:2022
- 资助金额:
$ 18.65万 - 项目类别:
The Functional Implications of Astrocytic GPCR-signaling on Alcohol Abuse
星形胶质细胞 GPCR 信号传导对酒精滥用的功能影响
- 批准号:
10472456 - 财政年份:2021
- 资助金额:
$ 18.65万 - 项目类别:
The Functional Implications of Astrocytic GPCR-signaling on Alcohol Abuse
星形胶质细胞 GPCR 信号传导对酒精滥用的功能影响
- 批准号:
10089613 - 财政年份:2021
- 资助金额:
$ 18.65万 - 项目类别:
The Functional Implications of Astrocytic GPCR-signaling on Alcohol Abuse
星形胶质细胞 GPCR 信号传导对酒精滥用的功能影响
- 批准号:
10673854 - 财政年份:2021
- 资助金额:
$ 18.65万 - 项目类别:
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