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:
- 金额:$ 56.64万
- 依托单位:
- 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:
- 关键词:AddressAnimal BehaviorBehavioralBrainBrain DiseasesCRISPR/Cas technologyCell NucleusCellsCessation of lifeChronicCocaineCocaine DependenceCoupledDNA MethylationDNA Modification MethylasesDataData SetDependovirusDevelopmentDiseaseDopamineDoseDrug AddictionElectrophysiology (science)Epigenetic ProcessExtinction (Psychology)FluorescenceGene ExpressionGenesGoalsHealthHerpesvirus 1HeterogeneityHumanIntravenousKnock-outLabelMaintenanceMediatingMethyl-CpG-Binding Protein 2ModelingMolecularMusNational Institute of Drug AbuseNeuronsPharmaceutical PreparationsPhasePlayPopulationProcessPsychological reinforcementRNA analysisRelapseRewardsRoleSelf AdministrationSorting - Cell MovementSystemTechniquesTranscriptional RegulationUnited StatesVentral Tegmental AreaViraladdictionbasebisulfite sequencingclinically relevantcocaine self-administrationcomparativecostdopaminergic neurondrug of abuseepigenetic regulationgenetic approachgenetic manipulationhistone modificationmethylomenew therapeutic targetnovelrelapse riskresponsesocialtranscriptometranscriptome sequencingweb sitewhole 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:
- 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:
- 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:
- 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。
- DOI:10.1016/j.celrep.2017.03.004
- 发表时间:2017-03-28
- 期刊:
- 影响因子:8.8
- 作者:Chen R;Wu X;Jiang L;Zhang Y
- 通讯作者:Zhang Y
A molecularly defined D1 medium spiny neuron subtype negatively regulates cocaine addiction.
- DOI:10.1126/sciadv.abn3552
- 发表时间:2022-08-12
- 期刊:
- 影响因子:13.6
- 作者:
- 通讯作者:
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Arginyl-tRNA beyond translation: mechanism and regulation of protein arginylation
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- 批准号:
10711167 - 财政年份:2023
- 资助金额:
$ 56.64万 - 项目类别:
A Wireless, Multimodal Neural Probe for Simultaneous Membrane-Free Neurochemical Sampling and Neuropharmacology
用于同步无膜神经化学采样和神经药理学的无线多模态神经探针
- 批准号:
10521971 - 财政年份:2022
- 资助金额:
$ 56.64万 - 项目类别:
A Wireless, Multimodal Neural Probe for Simultaneous Membrane-Free Neurochemical Sampling and Neuropharmacology
用于同步无膜神经化学采样和神经药理学的无线多模态神经探针
- 批准号:
10646362 - 财政年份:2022
- 资助金额:
$ 56.64万 - 项目类别:
Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
- 批准号:
10115270 - 财政年份:2021
- 资助金额:
$ 56.64万 - 项目类别:
Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
- 批准号:
10381647 - 财政年份:2021
- 资助金额:
$ 56.64万 - 项目类别:
Understanding neuronal subtype-specific function of NAc in cocaine addiction
了解 NAc 在可卡因成瘾中的神经元亚型特异性功能
- 批准号:
10569638 - 财政年份:2021
- 资助金额:
$ 56.64万 - 项目类别:
A Wireless, Closed-Loop Neural Probe for Optogenetics, Pharmacology and Neurochemical Monitoring
用于光遗传学、药理学和神经化学监测的无线闭环神经探针
- 批准号:
10320710 - 财政年份:2020
- 资助金额:
$ 56.64万 - 项目类别:
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