Adolescent Binge Ethanol Dysregulation of H3K36me3 Leads to Cryptic Transcription and Lasting Memory Deficits

青少年暴饮乙醇 H3K36me3 失调导致隐性转录和持久记忆缺陷

基本信息

  • 批准号:
    10314644
  • 负责人:
  • 金额:
    $ 4.16万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-09-25 至 2024-09-24
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY The prefrontal cortex (PFC) undergoes significant changes during adolescence, and alcohol exposure during this time is particularly damaging. Consuming alcohol, especially in binges, has been shown to negatively impact the adolescent brain, resulting in brain structural changes and lasting deficits in attention, visuospatial skills, and memory. The underlying mechanisms of these deficits are largely unknown; however, histone epigenetic regulation of gene expression provides an attractive mechanism for driving long-term behavioral and cognitive changes following binge ethanol. Through interaction with environmental stimuli, such as alcohol, epigenetic alterations can determine downstream gene expression, which in turn affects behavioral outcomes. The proposed study will investigate whether histone epigenetic alterations are the mechanism behind the persistent memory deficits of adolescents exposed to binge levels of ethanol. Specifically, the study will focus on tri-methylated histone 3, lysine 36 (H3K36me3). H3K36me3 has been shown to be affected by adolescent binge ethanol, and also plays significant roles in transcription regulation and memory function. These functional roles may provide a mechanism for how dysregulation of H3K36me3 by adolescent binge ethanol could underlie long-term memory deficits. Additionally, H3K36me3 is an under-studied mark, and further investigation of its role in memory function and cryptic transcription will provide valuable data for others involved in behavioral epigenetic research. Through this proposal, we intend to determine how H3K36me3-regulated loci and gene expression patterns within the PFC are altered after adolescent binge ethanol. By overlaying chromatin immunoprecipitation (ChIP) sequencing with RNA sequencing data, we will determine how ethanol- induced dysregulation of H3K36me3 affects gene expression, and at which loci these changes are occurring. We also plan to manipulate H3K36me3 levels within the PFC to determine if altering this epigenetic mark can change the behavioral outcomes of adolescent binge ethanol. These studies therefore have the potential to expand the knowledge of how epigenetic alterations can induce lasting behavioral changes. The success of these epigenetic and genomic studies will identify novel genes that might contribute to the persistent memory deficits associated with adolescent binge ethanol, which could ultimately lead to pharmaceutical targets to reverse cognitive deficits associated with adolescent binge drinking. Additionally, this study will facilitate my training in molecular techniques, bioinformatics analyses, and animal behavior models. In addition to the critical thinking, scientific writing, and professional development skills that I will be trained in, this research will prepare me to become a successful independent researcher studying how environmental influences, such as alcohol consumption, is encoded into the epigenome and how this can cause lasting impacts to behavior.
项目总结 前额叶皮质(PFC)在青春期和酒精暴露期间经历了显著的变化 这一次尤其具有破坏性。饮酒,特别是在狂欢中,已经被证明是负面的。 影响青少年的大脑,导致大脑结构的变化和注意力、视觉空间的持久缺陷 技能和记忆力。这些缺陷的潜在机制在很大程度上是未知的;然而,组蛋白 基因表达的表观遗传调控为驱动长期行为提供了一种诱人的机制 以及酗酒后的认知变化。通过与环境刺激的相互作用,如酒精, 表观遗传改变可以决定下游基因的表达,进而影响行为结果。 这项拟议的研究将调查组蛋白表观遗传改变是否是导致 暴露在过量酒精中的青少年的持久性记忆缺陷。具体地说,这项研究将集中在 三甲基化组蛋白3,赖氨酸36(H3K36me3)。H3K36me3已被证明受到青少年的影响 酗酒,在转录调控和记忆功能中也发挥着重要作用。这些功能 角色可能为青少年酗酒导致H3K36me3的失调提供了一种机制 这是长期记忆缺陷的根源。此外,H3K36me3是一个正在研究中的标记,并将进行进一步的研究 它在记忆功能和密码转录中的作用将为其他相关研究提供有价值的数据 行为表观遗传学研究。通过这项提议,我们打算确定H3K36me3基因如何调节基因座 青少年酗酒后,PFC内的基因表达模式发生了变化。通过叠加 染色质免疫沉淀(ChIP)测序与RNA测序数据,我们将确定乙醇如何- H3K36me3的诱导失调会影响基因的表达,以及这些变化发生在什么位置。 我们还计划在PFC内操纵H3K36me3水平,以确定改变这种表观遗传标记是否可以 改变青少年酗酒的行为结果。因此,这些研究有可能 扩展关于表观遗传改变如何导致持久的行为改变的知识。的成功之处 这些表观遗传学和基因组研究将确定可能有助于持久记忆的新基因 与青少年酗酒有关的缺陷,这最终可能导致药物靶点 逆转与青少年酗酒相关的认知缺陷。此外,这项研究将有助于我的 分子技术、生物信息学分析和动物行为模型方面的培训。除 我将接受的批判性思维、科学写作和职业发展技能,这项研究将 让我做好准备,成为一名成功的独立研究员,研究环境影响,如 酒精消费,被编码在表观基因组中,以及这如何对行为造成持久的影响。

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 }}

Emily Rose Brocato其他文献

Emily Rose Brocato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 }}

{{ truncateString('Emily Rose Brocato', 18)}}的其他基金

Adolescent Binge Ethanol Dysregulation of H3K36me3 Leads to Cryptic Transcription and Lasting Memory Deficits
青少年暴饮乙醇 H3K36me3 失调导致隐性转录和持久记忆缺陷
  • 批准号:
    10569496
  • 财政年份:
    2021
  • 资助金额:
    $ 4.16万
  • 项目类别:

相似海外基金

Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
  • 批准号:
    23K09542
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The impact of changes in social determinants of health on adolescent and young adult mental health during the COVID-19 pandemic: A longitudinal study of the Asenze cohort in South Africa
COVID-19 大流行期间健康社会决定因素的变化对青少年和年轻人心理健康的影响:南非 Asenze 队列的纵向研究
  • 批准号:
    10755168
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
A Priority Setting Partnership to Establish a Patient, Caregiver, and Clinician-identified Research Agenda for Adolescent and Young Adult Cancer in Canada
建立优先合作伙伴关系,以建立患者、护理人员和临床医生确定的加拿大青少年和年轻人癌症研究议程
  • 批准号:
    480840
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Miscellaneous Programs
Incidence and Time on Onset of Cardiovascular Risk Factors and Cardiovascular Disease in Adult Survivors of Adolescent and Young Adult Cancer and Association with Exercise
青少年和青年癌症成年幸存者心血管危险因素和心血管疾病的发病率和时间以及与运动的关系
  • 批准号:
    10678157
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
Fertility experiences among ethnically diverse adolescent and young adult cancer survivors: A population-based study
不同种族青少年和年轻成年癌症幸存者的生育经历:一项基于人群的研究
  • 批准号:
    10744412
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
Treatment development for refractory leukemia using childhood/adolescent, and young adult leukemia biobank
利用儿童/青少年和青年白血病生物库开发难治性白血病的治疗方法
  • 批准号:
    23K07305
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular design of Two-Way Player CAR-T cells to overcome disease/antigen heterogeneity of childhood, adolescent, and young adult cancers
双向 CAR-T 细胞的分子设计,以克服儿童、青少年和年轻成人癌症的疾病/抗原异质性
  • 批准号:
    23H02874
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Effects of adolescent social isolation on adult decision making and corticostriatal circuitry
青少年社会隔离对成人决策和皮质纹状体回路的影响
  • 批准号:
    10756652
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
Adolescent trauma produces enduring disruptions in sleep architecture that lead to increased risk for adult mental illness
青少年创伤会对睡眠结构产生持久的破坏,从而导致成人精神疾病的风险增加
  • 批准号:
    10730872
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
Using Tailored mHealth Strategies to Promote Weight Management among Adolescent and Young Adult Cancer Survivors
使用量身定制的移动健康策略促进青少年和年轻癌症幸存者的体重管理
  • 批准号:
    10650648
  • 财政年份:
    2023
  • 资助金额:
    $ 4.16万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了