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: 9390574
• 负责人: JOANNE WEINBERG
• 金额: $ 16.54万
• 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 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9390574
• 关键词: Activities of Daily Living; Address; Adjuvant Arthritis; Adult; Alcohol consumption; Alcohol-Related Neurodevelopmental Disorder; Alcohols; Animal Model; Area; Autistic Disorder; 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; Recruitment Activity; Reporting; Research; Research Subjects; Risk; Role; Sampling; Schizophrenia; Seminal; Stress; Suggestion; System; Teratogenic effects; Ukraine; Validation; Work; alcohol effect; alcohol exposure; cohort; cytokine; disorder risk; experience; fetal programming; functional outcomes; immune function; inflammatory marker; insight; neurobehavioral; novel; offspring; physical conditioning; prenatal; prenatal influence; programs; 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.

众所周知，成人疾病或失调的风险受到产前/早期生活环境的影响。基础上