酒精和阿片类药物使用障碍中的不同基因表达模式导致背侧前额叶皮层内功能网络的一致变化
Martha MacDonald1, Pablo A S Fonseca2, Kory Johnson3
1Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY.
bioRxiv : the preprint server for biology
|May 15, 2024
概括
像酒精使用障碍 (AUD) 和阿片类药物使用障碍 (OUD) 这样的物质使用障碍共享共同的生物学途径,而不仅仅是基因. 这表明了针对炎症和突触可塑性的统一治疗的潜力.
科学领域:
- 神经科学是一个神经科学.
- 遗传学 遗传学 是一个
- 药理学 药理学是指药理学的学科.
背景情况:
- 包括酒精使用障碍 (AUD) 和阿片类药物使用障碍 (OUD) 在内的物质使用障碍 (SUD) 是普遍的,昂贵的,并且经常同时发生.
- 了解AUD和OUD的分子基础,特别是它们的共同发生,对于开发有效的治疗方法至关重要.
研究的目的:
- 通过基因组和转录组分析,研究与AUD和OUD相关的背侧前额叶皮层中保存和独特的分子通路.
- 探索AUD和OUD在基因和途径层面之间的分子机制的重叠和分歧.
- 将转录组发现与全基因组关联研究 (GWAS) 整合起来,以评估共享遗传性并确定潜在的治疗点.
主要方法:
- 对公共数据集进行了基因组和转录组分析.
- 基因表达模式的比较分析AUD和OUD在背侧前额叶皮层之间的基因表达模式.
- 将转录组数据与问题性酒精使用 (PAU) 和OUD的GWAS数据集成.
主要成果:
- 在AUD和OUD转录组之间的基因水平上观察到适度的重叠.
- 在共享的生物学途径上发现了实质性的趋同,包括炎症,突触可塑性和细胞内信号传递.
- GWAS集成证实了有限的共享遗传性,但证实了转录基因数据中发现的通路水平的融合.
结论:
- AUD和OUD表现出不同的基因水平的转录变化,但汇聚在共同的生物学途径上.
- 这些共同的途径代表了开发用于同时发生AUD和OUD的新疗法的有希望的目标.
相关概念视频
CNS Depressants: Alcohol and Nicotine
203
Ethanol, a clear colorless alcohol, has been consumed by humans for millennia, but its effects on the body are far from benign. At lower doses, it induces decreased inhibitions and loquaciousness, leading to its social appeal. However, it can cause severe consequences at higher doses, such as coma and respiratory depression, due to its zero-order elimination kinetics. Chronic ethanol abuse wreaks havoc on multiple organ systems, particularly the CNS and the liver. Abrupt cessation of ethanol...
203
Substance Use Disorders Affecting Sleep
165
Substance use disorders involve a pattern of using drugs more extensively than intended and continuing use despite harmful consequences. This includes legal substances like alcohol and nicotine, as well as illegal drugs. These disorders often involve both physical and psychological dependence, reflecting compulsive use of substances that significantly alter thoughts, feelings, and behaviors, contributing to a major public health issue.
Understanding the concepts of physical dependence,...
Understanding the concepts of physical dependence,...
165
Drug Abuse and Addiction: Pharmacological Phenomena
467
Drug dependence, abuse, and addiction are complex phenomena that can precipitate various abnormal states. Physical dependence refers to a state of pharmacological adaptation to a drug. This adaptation often results in tolerance—a reduced response to the drug after repeated administrations. When the drug use is abruptly stopped, withdrawal symptoms occur due to the body's need to readjust from the pharmacologically induced imbalance. However, tolerance and withdrawal symptoms do not...
467
Cell Specific Gene Expression
13.6K
Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
13.6K
Human Genetics
561
Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
The complex relationship between genetics and psychology is observable through common biological components such...
561
Opioid Receptors: Overview
749
Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
749


