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: 10540965
• 负责人: Simon Alexander Marshall
• 金额: $ 18.65万
• 依托单位: NORTH CAROLINA CENTRAL UNIVERSITY
• 依托单位国家: 美国
• 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: https://reporter.nih.gov/project-details/10540965
• 关键词: Address; Affect; Alcohol consumption; Alcohol dependence; Alcohols; Anti-Inflammatory Agents; Area; Astrocytes; Attenuated; Behavior; Behavioral; Biological Assay; Brain; Brain Injuries; Brain-Derived Neurotrophic Factor; Cells; Cognitive deficits; Consummatory Behavior; Consumption; Country; Dependence; Development; Enzyme-Linked Immunosorbent Assay; Ethanol; Ethanol dependence; Event; Functional disorder; Future; G Protein-Coupled Receptor Signaling; GLAST Protein; Glial Fibrillary Acidic Protein; Glutamate Transporter; Glutamates; Grant; Heavy Drinking; Hippocampus (Brain); Human; Immune; Immunocompetent; Immunohistochemistry; Incidence; Inflammatory; Interleukin-1; Interleukin-1 beta; Interleukin-10; Intoxication; Lead; Link; Measures; Mediating; Memory; Memory impairment; Microdialysis; Minority; Modeling; Molecular; Morphology; Mus; Neuroimmune; Neuroimmune system; Neuroimmunomodulation; Neuronal Plasticity; Phenotype; Play; Procedures; Quantitative Reverse Transcriptase PCR; Receptor Signaling; Regulation; Reporting; Research; Risk; Role; Sex Differences; Signal Transduction; Site; Testing; United States; Viral; Work; alcohol abuse therapy; alcohol effect; alcohol research; alcohol use disorder; anakinra; binge drinking; combat; cytokine; designer receptors exclusively activated by designer drugs; drinking; experimental study; extracellular; glutamatergic signaling; health disparity; health economics; improved; innovation; insight; neuroinflammation; neurotransmission; novel; novel therapeutics; object recognition; prevent; response; sex; socioeconomics; synaptic function; uptake

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：过度狂饮酒精会引起重大的健康和社会经济问题