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

Role of DNA Methylation in Cocaine Addiction

DNA 甲基化在可卡因成瘾中的作用

基本信息

批准号：
10113569
负责人：
Yi Zhang
金额：
$ 56.64万
依托单位：
BOSTON CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-04-01 至 2023-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10113569
关键词：
Address Animal Behavior Behavioral Brain Brain Diseases CRISPR/Cas technology Cell Nucleus Cells Cessation of life Chronic Cocaine Cocaine Dependence Coupled DNA Methylation DNA Modification Methylases Data Data Set Dependovirus Development Disease Dopamine Dose Drug Addiction Electrophysiology (science)Epigenetic Process Extinction (Psychology)Fluorescence Gene Expression Genes Goals Health Herpesvirus 1 Heterogeneity Human Intravenous Knock-out Label Maintenance Mediating Methyl-CpG-Binding Protein 2 Modeling Molecular Mus National Institute of Drug Abuse Neurons Pharmaceutical Preparations Phase Play Population Process Psychological reinforcement RNA analysis Relapse Rewards Role Self Administration Sorting - Cell Movement System Techniques Transcriptional Regulation United States Ventral Tegmental Area Viral addiction base bisulfite sequencing clinically relevant cocaine self-administration comparative cost dopaminergic neuron drug of abuse epigenetic regulation genetic approach genetic manipulation histone modification methylome new therapeutic target novel relapse risk response social transcriptome transcriptome sequencing web site whole genome

项目摘要

Role of DNA methylation in cocaine addiction Abstract Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug seeking and use despite harmful consequences. It is an urgent social and health problem contributing to more than 90,000 deaths and incurs a yearly cost of over $700 billion in the United States (see NIDA website). It is believed that long-term maladaptive changes in the mesolimbic dopamine reward system play a central role in the development of addictive disorders. However, the underlying molecular mechanism remains largely unknown. The long-lasting effect of drugs on animal behavior and the risk of relapse in human addicts indicate that some stable changes in the brain reward system induced by drugs of abuse mediate these long-term behavioral adaptions. Accordingly, accumulating evidence suggests that drug-induced epigenetic changes, particularly DNA methylation and histone modifications changes, play important roles in drug addiction. However, due to technical difficulties in dealing with the cellular heterogeneity of the mammalian brain, most of the molecular studies performed so far used mixed cell populations, making interpretation of the available data difficult. Consequently, limited progress has been made in understanding the molecular basis of drug addiction. To overcome the issue of cell heterogeneity and to advance our understanding of the epigenetic mechanisms underlying drug addiction, we propose to comprehensively analyze the role of DNA methylation in drug addiction in a neuron subtype- and projection-specific manner using a clinically relevant intravenous cocaine self-administration (IVSA) model. Specifically, we seek to elucidate how DNA methylation in ventral tegmental area (VTA) dopaminergic neurons regulates cocaine reinforcement. To achieve this goal, we have established the following specific aims: 1) Profile transcriptome and methylome of VTA dopaminergic (DA) neurons using a mouse cocaine IVSA model; 2) Functional analysis of key genes regulating DNA methylation in VTA DA neurons; 3) Understand the role of DNA methylation in cocaine reinforcement in projection-specific VTA DA neurons. Completion of the proposed study will not only advance our understanding of how DNA methylation contributes to drug addiction, but also reveal novel therapeutic targets for treating this disorder. Importantly, our study provides a novel, broadly applicable strategy for understanding epigenetic regulation in a neuron subtype- and projection-specific manner.

DNA甲基化在可卡因成瘾中的作用

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain.

DOI：
10.1038/s41593-023-01455-9
发表时间：
2023-11
期刊：
NATURE NEUROSCIENCE
影响因子：
25
作者：
Bhattacherjee, Aritra;Zhang, Chao;Watson, Brianna R.;Djekidel, Mohamed Nadhir;Moffitt, Jeffrey R.;Zhang, Yi
通讯作者：
Zhang, Yi

Accurate inference of genome-wide spatial expression with iSpatial.

DOI：
10.1126/sciadv.abq0990
发表时间：
2022-08-26
期刊：
Science advances
影响因子：
13.6
作者：
通讯作者：

In vivo nuclear capture and molecular profiling identifies Gmeb1 as a transcriptional regulator essential for dopamine neuron function.

体内核捕获和分子分析将 Gmeb1 确定为多巴胺神经元功能必需的转录调节因子。

DOI：
10.1038/s41467-019-10267-0
发表时间：
2019
期刊：
Nature communications
影响因子：
16.6
作者：
Tuesta,LuisM;Djekidel,MohamedN;Chen,Renchao;Lu,Falong;Wang,Wengang;Sabatini,BernardoL;Zhang,Yi
通讯作者：
Zhang,Yi

Single-Cell RNA-Seq Reveals Hypothalamic Cell Diversity.

单细胞RNA-Seq揭示了下丘脑细胞的多样性。