RNA splicing regulation during alcohol withdrawal

酒精戒断过程中的 RNA 剪接调节

基本信息

项目摘要

Project Summary/Abstract One way in which chronic alcohol exposure produces neuronal adaptations is by changing gene expression. These changes can influence alcohol-drinking behavior and may lead to the development of alcohol use disorder (AUD). Additionally, during alcohol withdrawal, gene expression changes can contribute to the development of negative affective states, such as anxiety and depression, which makes it challenging for individuals to stop consuming alcohol. Mounting evidence from many species indicates that chronic a lcohol exposure also leads to alternatively spliced transcripts in different brain regions. Yet the molecular mechanisms by which alcohol alters RNA splicing remains unknown. This K99/R00 award includes a comprehensive career development and research plan based on Dr. Luana Carvalho’s preliminary data showing that withdrawal from chronic alcohol exposure in male rats increases the expression of genes encoding components of the RNA splicing machinery and leads to changes in RNA splicing. My preliminary data shows increased expression of the splicing factor Poly r(C) binding protein (PCBP1) in the hippocampus (HPC) of ethanol withdrawn rats that present with anxiety and depression-like behavior, as well as in the postmortem HPC of subjects diagnosed with AUD. I also found that PCBP1 is implicated in the mis-splicing of the Hapln2 gene, an important regulator of neuronal conductivity in which loss of function could negatively impact neurotransmission in the context of alcohol use. The scientific goal of this K99/R00 is to investigate RNA splicing, with a focus on PCBP1, as a mechanism by which chronic alcohol exposure and withdrawal leads to molecular alterations and contributes to the emergence of negative affective states. I will manipulate PCBP1 expression using viral-mediated gene delivery to test its behavioral relevance during alcohol withdrawal. I will also perform RNA immunoprecipitation with a PCBP1 antibody, followed by next generation sequencing to identify PCBP1-targets. Finally, I will perform full-length transcriptome sequencing to identify the portfolio of alternatively spliced transcripts in the HPC during chronic alcohol exposure and withdrawal. During my K99 phase, I will gain additional technical training in cutting-edge molecular, bioinformatic and statistical approaches. I will also enhance my leadership skills and receive considerable training in grant writing, oral presentations, and ethics that will be crucial to my success as an independent researcher. During the R00 phase, I will apply all training received to continue this project and further explorer PCBP1 targets in the HPC of humans diagnosed with AUD. Collectively, this work will provide insights into the molecular mechanisms underlying alcohol withdrawal-induced changes on RNA splicing and negative affective states, reveal novel targets and testable hypothesis for future functional studies, and facilitate translational research for finding new targets for AUD treatment.
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Luana Martins Carvalho其他文献

Luana Martins Carvalho的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

相似海外基金

The investigation of chronic alcohol consumption enhanced aging colon in elder mice and the mechanism of suppressed on aging colon tissues by sesame lignans continuous intake
长期饮酒促进老年小鼠结肠衰老的研究及持续摄入芝麻木脂素抑制结肠组织衰老的机制
  • 批准号:
    23K10904
  • 财政年份:
    2023
  • 资助金额:
    $ 14.97万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms of carcinogenesis and symptoms associated with alcohol consumption
致癌的分子机制和饮酒相关症状
  • 批准号:
    23K05734
  • 财政年份:
    2023
  • 资助金额:
    $ 14.97万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Internal Sources of Minority Stress and Alcohol Consumption
少数群体压力和饮酒的内部根源
  • 批准号:
    10742318
  • 财政年份:
    2023
  • 资助金额:
    $ 14.97万
  • 项目类别:
Characterizing the Relationship Between Alcohol Consumption and Neuron-Derived Exosomal MicroRNA Cargo in an Adolescent-Young Adult Twin Cohort
青少年双胞胎队列中酒精消耗与神经元衍生的外泌体 MicroRNA 货物之间关系的表征
  • 批准号:
    10452928
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
Endocrine regulation of alcohol consumption and fear learning
饮酒和恐惧学习的内分泌调节
  • 批准号:
    10483780
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
The impact of friends sharing different modalities of alcohol-related social media content on alcohol consumption: A longitudinal examination of changes in content shared by social networks over time
朋友分享不同形式的酒精相关社交媒体内容对饮酒的影响:对社交网络分享内容随时间变化的纵向研究
  • 批准号:
    10534428
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
  • 批准号:
    10339931
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
Cannabis' Impact on Alcohol Consumption: Integrating Laboratory and Ecological Momentary Assessment Methods
大麻对酒精消费的影响:整合实验室和生态瞬时评估方法
  • 批准号:
    10595096
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
Chronic alcohol consumption results in elevated Autotaxin levels that suppress anti-tumor immunity
长期饮酒会导致自分泌运动因子水平升高,从而抑制抗肿瘤免疫力
  • 批准号:
    10370159
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
Characterizing the Relationship Between Alcohol Consumption and Neuron-Derived Exosomal MicroRNA Cargo in an Adolescent-Young Adult Twin Cohort
青少年双胞胎队列中酒精消耗与神经元衍生的外泌体 MicroRNA 货物之间关系的表征
  • 批准号:
    10613564
  • 财政年份:
    2022
  • 资助金额:
    $ 14.97万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了