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: 8265941
• 负责人: Henrik Druid
• 金额: $ 33.04万
• 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/8265941
• 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.

描述（由申请人提供）：成瘾神经元的碳-14出生日期人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，新的神经元不仅在整个生命过程中产生，它们还整合到大脑的回路中，并在整个生命过程中积极参与其功能。通过将生物医学方法与加速器质谱（AMS）的最新发展相结合，现在可以测量来自地上核弹试验的环境14 C在神经元DNA中的掺入。我们建议使用这种新的方法来回顾性地确定成年人脑细胞的出生日期，并测试滥用药物和酒精对细胞周转的影响。这一建议是支持我们访问一个大型的存档生物储存库的特点良好的死后大脑标本从慢性物质滥用者。我们的假设是，成瘾是一种损害成人大脑神经干细胞和祖细胞库的情况。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整个生命周期中成人产生的神经元的影响。成瘾药物或酒精的慢性滥用可能会影响干/祖细胞库，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。我们建议映射网站的神经发生在成年人大脑的选择区域，以确定不同类别的滥用物质对细胞周转的影响，使用14 C出生日期的方法和AMS与免疫学检测的早期命运和增殖标记平行。药物或酒精诱导的海马神经发生的变化可能是导致强迫性使用和戒断失败的顽固性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型治疗方法具有重要意义。