权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Impact of chronic alcohol on neuronal cholinergic signaling

慢性酒精对神经元胆碱能信号的影响

基本信息

批准号：
10667844
负责人：
Armando Salinas
金额：
$ 14.6万
依托单位：
LOUISIANA STATE UNIV HSC SHREVEPORT
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-15 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10667844
关键词：
Ablation Acetylcholine Acetylcholinesterase Age Agreement Alcohol consumption Alcohols Autopsy Axon Behavior Behavioral Brain Brain region Choline Choline O-Acetyltransferase Cholinergic Agonists Cholinergic Receptors Chronic Cognitive Congenital Abnormality Corpus striatum structure Data Disease Dopamine Economic Burden Electrodes Enzymes Female Gene Expression Genes Grant Heart Hydrogen Peroxide Immune system Impaired cognition Lead Link Literature Liver diseases Macaca Macaca mulatta Measurement Measures Medial Mediating Methods Monkeys Mus Muscarinic Acetylcholine Receptor Muscarinics Neurobiology Neurologic Neurons Neurotransmitters Nicotinic Receptors Occupations Oregon Oxidases Patients Pattern Periodicity Phenotype Polymers Prefrontal Cortex Primates Proteins RNA Receptor Gene Recording of previous events Relapse Research Resources Rodent Role Sampling Scanning Self Administration Signal Transduction Slice Source Surface Tissue Banks Tissues Work acetylcholine transporter adverse outcome alcohol craving alcohol exposure alcohol seeking behavior alcohol use disorder basal forebrain behavioral phenotyping biomaterial compatibility brain tissue carbon fiber caudate nucleus cholinergic cholinergic neuron chronic alcohol ingestion cingulate cortex economic impact experience experimental study fabrication flexibility health economics human model interest male neurotransmission novel psychologic putamen receptor expression socioeconomics temporal measurement transmission process varenicline

项目摘要

Project Summary Alcohol use disorder (AUD) is a chronic condition characterized by escalating alcohol intake, preoccupation with alcohol, and continued alcohol use despite adverse consequences. AUD has broad negative health and socioeconomic impacts. AUD is linked to liver disease, birth defects, neurological and psychological complications, weakened immune system, and heart problems. In the US, the economic burden of AUD exceeds $220 billion annually. One facet of AUD is persistent engagement in deleterious behaviors (e.g. alcohol consumption). The inability to alter these behaviors may be due to chronic alcohol-induced deficits in acetylcholine (ACh) signaling. Interestingly, ablation of ACh neurons results in AUD-like behavioral phenotypes. Thus, the experiments proposed in this grant will examine ACh signaling in tissues obtained from rhesus macaques with a history of long-term alcohol self-administration. In the first experiment, the fabrication method for carbon fiber electrodes to measure ACh release will be refined and validated for measurement of ACh release in mouse brain slices (Specific Aim 1a). These validated acetylcholine probes will then be used in two annual necropsies at the Oregon National Primate Research Center where we will measure ACh release in brain regions implicated in AUD (e.g. caudate nucleus, putamen, cingulate & prefrontal cortex) from long-term alcohol self-administering and control macaques (Specific Aim 1b). In the second set of experiments (Specific Aim 2), we will obtain RNA samples from several brain regions from the Monkey Alcohol Tissue Research Resource (MATRR) to compare gene expression of ACh signaling related proteins from the same alcohol self-administering and control macaques used in the necropsies. Altogether, the subjects from these necropsies will include male and female, as well as, alcohol self-administering and control subjects, allowing for multifactorial analysis of any obtained data. Further, our ACh measurements will be correlated with cognitive flexibility measures obtained by the MATRR. Importantly, these results will fill a gap in the AUD literature and make use of an important resource (MATRR) that provides NHP tissues from the most relevant and translatable model of human AUD.

项目总结