Effects of air pollution/maternal stress on microglial sculpting of social circuits

空气污染/母亲压力对社会回路小胶质细胞塑造的影响

基本信息

  • 批准号:
    10283978
  • 负责人:
  • 金额:
    $ 9.53万
  • 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:
    2021-08-06 至 2023-07-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Autism spectrum disorder (ASD) currently affects 1 in 59 children in the United States, 80% of whom are male, and is characterized primarily by impaired social interaction/communication. Prenatal exposure to air pollution has been implicated in the etiology of ASD, as well as many other neuropsychiatric disorders. However, the mechanisms by which air pollution alters the development of social circuits in the brain remains unknown. Importantly, there are large social disparities in environmental toxin exposure whereby marginalized communities bear the greatest burden of exposure. Using a novel mouse model that combines an environmental toxin (diesel exhaust particles; DEP) with an ethologically relevant maternal stressor (resource deprivation; MS), our preliminary data show that these exposures in combination, but neither alone, induce robust deficits in social interaction in male, but not female offspring. This is line with a model in which maternal psychosocial stress unmasks vulnerability to environmental toxins in offspring. ASD is increasingly recognized as a whole-body disorder. Gastrointestinal symptoms and changes in the composition of the gut microbiome are present in more than 50% of individuals with ASD. Studies using animal models suggest a causal link between the gut microbiome and social behavior, but this has not been studied in the context of environmental toxins. During the K99 phase of this proposal, in Aim 1, I propose to further my training in the analysis of the gut microbiome to ask whether cross-fostering of DEP/MS pups at birth can prevent shifts in the gut microbiome (assessed using metagenomic sequencing). The dopamine system supports social interaction, is sensitive to microbial signaling, and my preliminary data suggests is down-regulated following DEP/MS exposure. Thus, in Aim 2, I propose to learn in vivo optogenetic techniques to test whether activation of the mesolimbic dopamine reward pathway is sufficient to restore social behavior following DEP/MS. During the R00 phase, in Aim 3, I will use the techniques acquired during the K99 phase to determine whether changes in the gut microbiome are responsible for changes in social behavior and dopamine signaling in DEP/MS offspring. Moreover, I will use the preliminary data gathered in Aim 1 to ask what potential metabolites or molecular mechanisms might be altered following DEP/MS. Finally, I will ask whether microglia, the resident immune cells of the brain, play a key role in mediating these microbiome-driven changes. Together, these experiments will elucidate the ways in which pollutants and stress synergize to produce dysregulation of the gut-brain axis and deficits in social behavior. This proposal will significantly advance my career development by providing me with new training in cutting-edge techniques such as in vivo optogenetics and metagenomic sequencing. Thus, it will help me to establish my own independent line of work and the preliminary data obtained herein will serve as a foundation for future R01 funding.
项目总结

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 }}

Caroline Jackson Smith其他文献

Caroline Jackson Smith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('Caroline Jackson Smith', 18)}}的其他基金

Effects of air pollution/maternal stress on microglial sculpting of social circuits
空气污染/母亲压力对社会回路小胶质细胞塑造的影响
  • 批准号:
    10748065
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
Effects of air pollution/maternal stress on microglial sculpting of social circuits
空气污染/母亲压力对社会回路小胶质细胞塑造的影响
  • 批准号:
    10462810
  • 财政年份:
    2021
  • 资助金额:
    $ 9.53万
  • 项目类别:
The Microglial Developmental Index: A Novel Framework for Understanding the Role of Microglia in the Etiology of Autism Spectrum Disorder
小胶质细胞发育指数:了解小胶质细胞在自闭症谱系障碍病因学中的作用的新框架
  • 批准号:
    9761008
  • 财政年份:
    2019
  • 资助金额:
    $ 9.53万
  • 项目类别:

相似海外基金

Identification of Prospective Predictors of Alcohol Initiation During Early Adolescence
青春期早期饮酒的前瞻性预测因素的鉴定
  • 批准号:
    10823917
  • 财政年份:
    2024
  • 资助金额:
    $ 9.53万
  • 项目类别:
Socio-Emotional Characteristics in Early Childhood and Offending Behaviour in Adolescence
幼儿期的社会情感特征和青春期的犯罪行为
  • 批准号:
    ES/Z502601/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.53万
  • 项目类别:
    Fellowship
Cognitive and non-cognitive abilities and career development during adolescence and adult development: from the perspective of genetic and environmental structure
青春期和成人发展期间的认知和非认知能力与职业发展:从遗传和环境结构的角度
  • 批准号:
    23K02900
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Reasoning about Spatial Relations and Distributions: Supporting STEM Learning in Early Adolescence
空间关系和分布的推理:支持青春期早期的 STEM 学习
  • 批准号:
    2300937
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
    Continuing Grant
Does social motivation in adolescence differentially predict the impact of childhood threat exposure on developing suicidal thoughts and behaviors
青春期的社会动机是否可以差异预测童年威胁暴露对自杀想法和行为的影响
  • 批准号:
    10785373
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
Mapping the Neurobiological Risks and Consequences of Alcohol Use in Adolescence and Across the Lifespan
绘制青春期和整个生命周期饮酒的神经生物学风险和后果
  • 批准号:
    10733406
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
The Role of Sleep in the Relationships Among Adverse Childhood Experiences, Mental Health Symptoms, and Persistent/Recurrent Pain during Adolescence
睡眠在不良童年经历、心理健康症状和青春期持续/复发性疼痛之间关系中的作用
  • 批准号:
    10676403
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
Thalamo-prefrontal circuit maturation during adolescence
丘脑-前额叶回路在青春期成熟
  • 批准号:
    10585031
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
Interdisciplinary Perspectives on the Politics of Adolescence and Democracy
青少年政治与民主的跨学科视角
  • 批准号:
    EP/X026825/1
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
    Research Grant
Harnessing digital data to study 21st-century adolescence
利用数字数据研究 21 世纪青春期
  • 批准号:
    MR/X028801/1
  • 财政年份:
    2023
  • 资助金额:
    $ 9.53万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了