The Biological Basis of Alcohol-and Smoking-Induced Brain Injury

酒精和吸烟引起的脑损伤的生物学基础

基本信息

批准号：
7474773
负责人：
DIETER J MEYERHOFF
金额：
$ 65.67万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-08-01 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7474773
关键词：
Abstinence Accounting Adverse effects Affect Alcohol consumption Alcohol dependence Alcoholic beverage heavy drinker Alcoholism Alcohols Amino Acids Aminobutyric Acid Aminobutyric Acids Anisotropy Apolipoprotein E Arts Atrophic Basic Science Behavior Therapy Biological Biological Markers Blood flow Brain Brain Injuries Brain region Brain-Derived Neurotrophic Factor Butyric Acid Butyric Acids Cell membrane Cerebrospinal Fluid Cerebrovascular Circulation Choline Chronic Clinical Cognitive Cognitive deficits Creatine Data Dependence Diffusion Diffusion Magnetic Resonance Imaging Echo-Planar Imaging Education Epilepsy Fiber Functional disorder Future Genotype Glutamates Goals Human Individual Injury Intelligence Knowledge Lead Light Lipids Magnetic Resonance Magnetic Resonance Imaging Maintenance Measures Membrane Mental Depression Metabolic Methodology Modality Monitor Myelin N-acetylaspartate Neurobiology Neurocognition Neurocognitive Neuroglia Neurons Nicotine Dependence Nicotine Use Disorder Noise Outcome Measure Oxidative Stress Parietal Lobe Pathway interactions Perfusion Phosphocreatine Physiologic pulse Play Process Public Health Education Pulse taking Rate Recovery Recovery of Function Relapse Reporting Research Research Personnel Rewards Role Signal Transduction Smoke Smoking Smoking Status Spin Labels Structure Substance Addiction Substance abuse problem Surrogate Markers Techniques Testing Time Translational Research Treatment outcome Ventral Tegmental Area Week alcohol abstinence alcohol abuse therapy alcohol use disorder base brain morphology brain tissue cerebral atrophy chronic alcohol ingestion cigarette smoking clinically significant day drinking gamma-Aminobutyric Acid gray matter improved in vivo magnetic field magnetic resonance spectroscopic imaging morphometry neural circuit neurochemistry neurocognitive test neuroimaging neuropathology neurotoxicity non-smoking novel strategies problem drinker programs response water diffusion white matter

项目摘要

DESCRIPTION (provided by applicant): Chronic cigarette smoking is very common in alcohol use disorders (AUD). Nevertheless, the effects of chronic smoking on in-vivo measures of brain injury in alcohol-dependent individuals have not been studied. Thus, it is unknown if the full extent of brain atrophy, cell membrane and microstructural injury, derangement of neurometabolism, low cerebral blood flow, and neurocognitive dysfunction described in alcohol dependence are solely attributable to chronic alcohol use, or if chronic smoking influences these measures. Preliminary results from our ongoing magnetic resonance (MR) and cognitive studies indicate that chronic smoking appears to exacerbate alcohol-induced abnormalities in brain morphology, neurochemistry, and blood flow, and may adversely affect recovery of surrogate markers of neuronal and cell membrane/myelin integrity as well as aspects of neurocognition during short-term abstinence from alcohol. The main goal of this competing continuation is therefore to test in treated alcohol dependent individuals (i) if chronic smoking compounds alcohol-induced neurobiological brain injury, (ii) if chronic smoking effects are functionally significant, and (iii) if chronic smoking influences recovery of alcohol-induced neurobiological and neurocognitive dysfunction during abstinence from alcohol. We will continue to apply an integrative approach of combining information from different MR modalities and neurocognitive testing in the same individual longitudinally to assess the neurobiological and functional consequences of chronic smoking in treated alcohol-dependent individuals. Specifically, we will continue our longitudinal 1.5 Tesla MR studies to quantitate regional brain structure, brain metabolites (reflecting neuronal and myelin viability), and regional cerebral blood flow as well as repeat comprehensive neurocognitive testing. In addition, new MR studies at high magnetic field (4T) will improve the quality of cerebral blood flow and diffusion data, and will measure cortical levels of glutamate and Y-aminobutyric acid, amino acids critically involved in the initiation and maintenance of substance dependence. Relationships of MR-derived and neurocognitive measures will determine the functional relevance of neurobiological measures and their changes over time and test the effects of chronic smoking on functional neurocircuitry in alcoholism. This application is responsive to PA-05-074 in that the proposed research will improve our understanding of the mechanisms underlying alcohol- and smoking induced brain injury and its potential reversibility with abstinence from alcohol. Chronic smoking may have hitherto unrecognized but significant contributions to these neurobiological processes and their cognitive and clinical consequences. The knowledge to be gained from this translational research can be used directly for public education, in new approaches to pharmacologic and behavioral interventions for AUD, and in monitoring treatment outcome.

描述（由申请人提供）：慢性吸烟在酒精使用障碍中非常普遍（AUD）。然而，尚未研究长期吸烟对酒精依赖性个体脑损伤体内措施的影响。因此，尚不清楚脑萎缩，细胞膜和微结构损伤的全部程度，神经代谢的危险，低脑血流的危险以及酒精依赖性中描述的神经认知功能障碍完全归因于长期归因于慢性酒精的使用，或者是否会影响慢性吸烟的影响。我们正在进行的磁共振（MR）和认知研究的初步结果表明，慢性吸烟似乎加剧了酒精诱导的脑形态学，神经化学和血液流动的异常，并且可能会不利地影响神经元和细胞膜/骨髓蛋白完整性的神经元和细胞整合的替代标志物以及Neurocknition的替代标记。因此，这种竞争延续的主要目标是在接受治疗的酒精依赖的个体中测试（i），如果慢性吸烟会使酒精引起的神经生物学脑损伤化合物，（ii）如果慢性吸烟在功能上具有重要意义，并且（iii）如果慢性吸烟会影响酒精诱导的神经生物学和神经认知能力疾病的恢复，则在酒精期间的恢复性降解。我们将继续采用一种综合方法，将来自不同MR模式和神经认知测试的信息结合在同一个体中，以评估治疗的酒精依赖性个体中慢性吸烟的神经生物学和功能后果。具体而言，我们将继续我们的纵向1.5 Tesla MR研究，以量化区域大脑结构，脑代谢产物（反映神经元和髓磷脂生存力）以及区域大脑血流以及重复全面的神经认知测试。此外，高磁场（4T）的新MR研究将改善脑血流量和扩散数据的质量，并将测量谷氨酸和Y-氨基丁酸的皮质水平，氨基酸与物质依赖性的启动和维持至关重要。 MR衍生和神经认知措施的关系将确定神经生物学措施及其随着时间的变化的功能相关性，并测试慢性吸烟对酒精中毒对功能性神经通律的影响。该应用对PA-05-074的响应有响应，因为拟议的研究将提高我们对酒精和吸烟引起的脑损伤的机制的理解，以及其潜在的可逆性，并戒酒。迄今为止，慢性吸烟可能对这些神经生物学过程及其认知和临床后果产生了重大贡献。从这项翻译研究中获得的知识可以直接用于公共教育，采用新的AUD药理和行为干预措施的方法以及监测治疗结果。