Carbon-14 birth dating of Neurons in addiction

成瘾神经元的碳 14 出生年代测定

• 批准号: 8098616
• 负责人: Henrik Druid
• 金额: $ 33.69万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8098616
• 关键词: Abstinence; Adult; Adverse effects; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Animals; Antidepressive Agents; Archives; Area; Autopsy; Biological; Biology; Biomedical Research; Birth; Brain; Brain region; C14 isotope; Cell Nucleus; Cells; Chronic; Cocaine; Cocaine Abuse; DNA; Date of birth; Development; Disease; Drug Addiction; Early Diagnosis; Forensic Pathology; Functional disorder; Health; Hippocampus (Brain); Human; Human body; Immunologics; Knowledge; Learning; Life; Link; Literature; Longevity; Maps; Measures; Memory; Methods; Nature; Nervous system structure; Neurobiology; Neuroglia; Neurons; Neurosciences Research; Neurotransmitters; Nuclear; Nuclear Physics; Opiates; Organism; Pathogenesis; Pharmaceutical Preparations; Population; Prefrontal Cortex; Primates; Process; Proliferating; Proliferation Marker; Regulation; Research; Rodent; Rodent Model; Role; Selective Serotonin Reuptake Inhibitor; Site; Specimen; Staging; Stem cells; Testing; Therapeutic Intervention; Time; Translating; accelerator mass spectrometry; addiction; drug of abuse; insight; monoamine; nerve stem cell; neurogenesis; novel strategies; novel therapeutic intervention; problem drinker; progenitor; regenerative; relating to nervous system; research study; stem; stem cell biology; substance abuser

DESCRIPTION (provided by applicant): Carbon-14 Birth Dating of Neurons in Addiction The dynamic turnover of neurons in the human brain is essentially unknown. Recent rodents and primates studies suggest that new neurons are not only generated throughout life, they integrate into the circuitry of the brain and actively participate in its functions throughout life. By combining biomedical approaches with recent developments in accelerator mass spectrometry (AMS), it is now possible to measure the incorporation of ambient 14C derived from above-ground nuclear bomb tests in neuronal DNA. We propose to use this novel approach to retrospectively establish the birth date of cells in adult human brain and to test for the effect of abused drugs and alcohol on cell turnover. This proposal is supported by our access to a large archived biorespository of well-characterized postmortem brain specimens from chronic substance abusers. Our hypothesis is that addiction is a condition that impairs the neural stem and progenitor cell pools in adult brain. A substantial literature describes the capacity of all addictive drugs to slow neurogenesis, but there are no studies, which have assessed the effect of abused drugs or alcohol on adult-generated neurons across the lifespan in humans. Chronic abuse of addictive drugs or alcohol may affect the stem/progenitor cell pool providing a link between dysfunctional neurogenesis and the pathobiology of addiction. We propose to map sites of neurogenesis in select regions of the adult brain to determine the effect of different classes of abused substances on cell turnover using the 14C birth dating method and AMS in parallel with immunologic detection of early fate and proliferation markers. Drug or alcohol-induced changes in hippocampal neurogenesis may be one of the underlying biological mechanisms responsible for the intractable cycle of compulsive use and failed abstinence. The proposed studies will contribute to an understanding of the neurobiology of drug and alcohol addiction, and may have important implications for the development of novel therapeutic approaches targeted to these cell populations. PUBLIC HEALTH RELEVANCE: Experimental studies in animals suggest that new neurons are generated throughout life, but it is not known if this is true in the human nervous system. We will employ a novel strategy to measure carbon-14 from nuclear bomb tests in DNA to birth date neurons in the human brain. These studies will provide insights into the biology of drug and alcohol addiction, as well as learning and memory.

描述（由申请人提供）：成瘾中神经元的碳-14出生年代测定人类大脑中神经元的动态更新基本上是未知的。最近对啮齿动物和灵长类动物的研究表明，新的神经元不仅在一生中产生，而且在一生中融入大脑回路并积极参与其功能。通过将生物医学方法与加速器质谱法（AMS）的最新发展相结合，现在可以测量神经元DNA中地面核弹试验产生的环境14C的含量。我们建议使用这种新方法来回顾性地确定成人大脑中细胞的出生日期，并测试滥用药物和酒精对细胞更新的影响。这一建议得到了我们对大型存档生物库的支持，这些生物库中有来自慢性药物滥用者的具有良好特征的死后脑标本。我们的假设是，成瘾是一种损害成人大脑神经系统和祖细胞池的情况。大量文献描述了所有成瘾药物减缓神经发生的能力，但没有研究评估滥用药物或酒精对人类一生中成年生成的神经元的影响。长期滥用成瘾性药物或酒精可能会影响干细胞/祖细胞池，从而在功能失调的神经发生和成瘾的病理生物学之间提供联系。我们建议在成人大脑的特定区域绘制神经发生位点，以确定不同类型的滥用物质对细胞更新的影响，使用14C出生测年法和AMS，同时使用免疫检测早期命运和增殖标志物。药物或酒精引起的海马神经发生变化可能是导致强迫性使用和戒断失败的顽固循环的潜在生物学机制之一。拟议的研究将有助于理解药物和酒精成瘾的神经生物学，并可能对开发针对这些细胞群的新治疗方法具有重要意义。