Immune Dysregulation in FASD: Programming of health and neurobehavioral outcomes

FASD 中的免疫失调：健康和神经行为结果的规划

• 批准号: 10165416
• 负责人: JOANNE WEINBERG
• 金额: $ 12.01万
• 依托单位: UNIVERSITY OF BRITISH COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-20 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165416
• 关键词: Activities of Daily Living; Address; Adjuvant Arthritis; Adult; Alcohol consumption; Alcohol-Related Neurodevelopmental Disorder; Alcohols; Animal Model; Area; Biological; Biological Markers; Birth; Blood specimen; Brain; British Columbia; Child; Childhood; Choline; Clinic; Cognitive; Collaborations; Competence; Data; Development; Dimensions; Disease; Environment; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Gene Expression; Grant; Health; Immune; Immune response; Immune system; Impaired cognition; Impairment; Individual; Infant; Inflammation; Inflammatory; Informal Social Control; Life; Life Cycle Stages; Link; Low Birth Weight Infant; Measures; Mental Health; Metabolic; Metabolic Diseases; Metabolic syndrome; Minnesota; Modeling; Mothers; Neurobiology; Neurocognition; Neurodevelopmental Disorder; Organism; Outcome; Pediatric Hospitals; Physiological; Plasma; Play; Predictive Factor; Pregnant Women; Psyche structure; Reporting; Research; Research Subjects; Risk; Role; Sampling; Schizophrenia; Seminal; Stress; Suggestion; System; Teratogenic effects; Ukraine; Validation; Work; alcohol effect; autism spectrum disorder; cohort; cytokine; disorder risk; early life adversity; experience; fetal programming; functional outcomes; immune function; inflammatory marker; insight; maternal alcohol use; neurobehavioral; novel; offspring; physical conditioning; prenatal; prenatal influence; programs; recruit; resilience; response

Risk for adult diseases or disorders is known to be influenced by the prenatal/early life environment. Building on seminal studies by Barker and colleagues, who reported associations between low birth weight and biological risk for adult disease, support for the “developmental origins of health and disease” (DOHaD) hypothesis has grown to include early life adversities beyond low birth weight and to extend to outcomes beyond metabolic syndrome. Of particular relevance, prenatal alcohol exposure (PAE), in addition to its teratogenic effects, can program developing neurobiological systems and thus increase risk for diseases/ disorders over the life course. Our CIFASD Developmental Project is the first to identify links among maternal alcohol consumption, inflammation, and child outcomes; unique immune signatures in pregnant women were identified in association with whether or not they consumed alcohol and with neurodevelopmental outcomes of their children. The proposed UO1 builds on these findings to examine immune profiles in pregnant women and children from birth through adulthood. Our working hypothesis is that prenatal alcohol-induced dysregulation of immune/ inflammatory systems will be associated with adverse health, functional and adaptive outcomes, providing insight into factors underlying risk and resilience. Specific Aims are to: 1) Use validation cohorts to confirm the utility of immune parameters as possible biomarkers and predictors of alcohol-related health and neurobehavioral outcomes, by analyzing: a) plasma samples and neurobehavioral outcomes from matched mother-infant or mother-child pairs from Ukraine (Chambers) and San Diego (Chambers, Jones, Mattson), respectively, and a child cohort from Minnesota (Wozniak). Assessment of individuals from different cultural/ethnic, SES, and environmental conditions will provide insight into factors modulating alcohol’s programming effects, and increase understanding of immune variables as biomarkers of alcohol intake and predictive factors for PAE-related outcomes. 2) Extend assessment of the immune system into adulthood with assessment of cohorts from Atlanta (Coles), Seattle (Grant), and British Columbia (Weinberg, Loock, Oberlander, Lutke). We will investigate whether physical/mental health and impaired cognitive and adaptive outcomes are associated with immune/inflammatory system dysregulation resulting from prenatal programming effects of alcohol. For both Aims, we will analyze cytokines/inflammatory markers in plasma, obtain past and current mental/physical health information, and measure neurobehavioral and adaptive outcomes, providing novel insight into links among immune function, cognitive and adaptive function, and health outcomes. Together, these studies bring a new dimension to CIFASD, a focus on DOHAD/health outcomes, a critically important but relatively understudied area. Moreover, as the immune system plays a key role in brain development, this work has broad implications for understanding the role of immune/inflammatory mechanisms in FASD-associated neurobehavioral and adaptive deficits.

已知成人疾病或疾病的风险受到产前/早期生活环境的影响。建立 Barker及其同事的开创性研究，他们报告了低出生体重与生物学之间的关联 成人疾病的风险，支持“健康与疾病的发展起源”（DOHAD）假设的支持已有 成长为包括早期生命力的早期逆境，超出了低出生体重，并扩展到新陈代谢之外的结果 综合征。特别相关，产前酒精暴露（PAE）除了其致畸作用外，还可以 计划开发神经生物学系统，从而增加生命过程中疾病/疾病的风险。 我们的CIFASD发展项目是第一个确定孕产妇饮酒之间的联系的项目， 炎症和儿童结局；鉴定出孕妇的独特免疫特征 他们是否消耗酒精以及孩子的神经发育结果。这 拟议的UO1建立在这些发现的基础上，以检查孕妇和儿童的免疫特征 通过成年。我们的工作假设是产前酒精诱导的免疫/ 炎症系统将与不利的健康，功能性和适应性结果相关联，提供洞察力 成为风险和弹性的基础因素。具体目的是：1）使用验证队列确认 免疫参数是可能的生物标志物和酒精相关健康和神经行为的预测因子 结果，分析：a）来自匹配的母亲或 分别来自乌克兰（钱伯斯）和圣地亚哥（钱伯斯，琼斯，马特森）的母子对 来自明尼苏达州（沃兹尼亚克）的儿童队列。评估来自不同文化/种族，SE和 环境条件将洞悉调节酒精编程效果的因素，并增加 理解免疫杂质作为酒精摄入量的生物标志物和与PAE相关的预测因素 结果。 2）通过评估亚特兰大的队列评估，将免疫系统的评估扩展到成年 （Coles），西雅图（Grant）和不列颠哥伦比亚省（Weinberg，Loock，Oberlander，Lutke）。我们将调查是否 身体/心理健康以及认知和适应性结果受损与免疫/炎症有关 饮酒产前编程效应引起的系统失调。对于这两个目标，我们将分析 血浆中的细胞因子/炎症标记，获得过去和当前的心理/身体健康信息，以及 测量神经行为和适应性结果，为免疫功能之间的联系提供新的见解， 认知和适应性功能以及健康结果。这些研究一起为 CIFASD是DOHAD/健康成果的关注，这是一个非常重要但相对了解的领域。而且， 由于免疫系统在大脑发育中起关键作用，因此这项工作对理解具有广泛的影响 免疫/炎症机制在FASD相关的神经行为和适应性缺陷中的作用。

项目成果

Prenatal Adversity Alters the Epigenetic Profile of the Prefrontal Cortex: Sexually Dimorphic Effects of Prenatal Alcohol Exposure and Food-Related Stress.

• DOI: 10.3390/genes12111773
• 发表时间: 2021-11-09
• 期刊: Genes
• 影响因子: 3.5
• 作者: Lussier AA;Bodnar TS;Moksa M;Hirst M;Kobor MS;Weinberg J
• 通讯作者: Weinberg J

Evidence for long-lasting alterations in the fecal microbiota following prenatal alcohol exposure.

• DOI: 10.1111/acer.14784
• 发表时间: 2022-04
• 期刊: ALCOHOL-CLINICAL AND EXPERIMENTAL RESEARCH
• 作者: Bodnar, Tamara S.;Lee, Christopher;Wong, Athena;Rubin, Ilan;Parfrey, Laura Wegener;Weinberg, Joanne
• 通讯作者: Weinberg, Joanne

Lack of Evidence for a Relationship Between Salivary CRP and Women's Sexual Desire: An Investigation Across Clinical and Healthy Samples.

• DOI: 10.1016/j.jsxm.2022.02.007
• 发表时间: 2022-05
• 期刊: JOURNAL OF SEXUAL MEDICINE
• 影响因子: 3.5
• 作者: Clephane, Kirstin;O'Loughlin, Julia I;Bodnar, Tamara S;Wilson, M Claire;Stariha, Jordan Tb;Craig, Amber N;Weinberg, Joanne;Brotto, Lori A;Lorenz, Tierney K
• 通讯作者: Lorenz, Tierney K