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Maternal ZIKV infection as an environmental risk factor for mental illness

母亲寨卡病毒感染是精神疾病的环境危险因素

基本信息

批准号：
10302543
负责人：
Brian Daniels
金额：
$ 22.57万
依托单位：
RUTGERS, THE STATE UNIV OF N.J.
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：
2021-07-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10302543
关键词：
Address Adult Adult Children Affect Attention Behavior Behavioral Brain Cognitive Development Developmental Gene DiGeorge Syndrome Environmental Risk Factor Etiology Expression Profiling Fetal Development Fetal Tissues Fetus Future Gene Expression Genes Genetic Genetic Predisposition to Disease Genetic Risk Immune Immune response Immune signaling Immunologics Individual Infection Inflammation Mediators Inflammatory Investigation Late pregnancy Life Link Maternal Health Maternal-Fetal Exchange Memory Mental Depression Mental Health Mental disorders Monitor Mood Disorders Motor Neuroimmune Neurologic Neurological outcome Outcome Pathogenicity Pathologic Pregnancy Proteins Psychoses Risk Factors Role Schizophrenia Shapes Signal Transduction Social Functioning Syndrome Virus Virus Diseases ZIKV infection Zika Virus antiviral immunity autism spectrum disorder behavior influence behavior test behavioral outcome cognitive function cytokine emerging pathogen fetal genetic risk factor human model immune activation mouse model neonate novel offspring pregnant social transcriptome sequencing tumor-immune system interactions

项目摘要

Abstract A large body of evidence has identified maternal immune activation following viral infection as an environmental risk factor for mental illness. Maternal immune signals, including inflammatory cytokines, can access fetal tissues and permanently alter brain function and behavior in otherwise developmentally normal offspring. Indeed, maternal infection with a number of viruses has been associated with the development of mood disorders and/or psychosis in offspring, and these associations are intensified in offspring with preexisting genetic risk factors for mental illness. Zika virus (ZIKV) is an emerging pathogen recently identified as an etiologic agent of severe neurodevelopmental syndromes following infection during the early stages of gestation. However, the impacts of maternal ZIKV infection during late gestation have not been adequately addressed, nor has the potential impact of maternal ZIKV infection on the mental health of developmentally normal offspring been investigated. Here, we propose to use a murine model of late-term maternal ZIKV infection to characterize neuroimmune signaling at the maternal-fetal interface. To study the consequences of this signaling, we will also assess the impact of late-term maternal ZIKV infection on the development of behavioral abnormalities in motor, cognitive and social domains that underlie psychiatric disorders (e.g., autism, schizophrenia). Finally, we will use an established mouse model of human 22q11.2 deletion syndrome, a common genetic susceptibility factor for mental illness, to examine interaction effects of maternal ZIKV infection with genetic risk for behavioral abnormalities. These studies will establish the potential pathologic behavioral consequences of late-term ZIKV infection, informing future study and monitoring efforts for individuals affected by this globally emerging pathogen.

摘要大量的证据已经确定病毒感染后母体免疫激活是一个重要的因素。精神疾病的环境风险因素。母体免疫信号，包括炎性细胞因子，进入胎儿组织并永久性地改变大脑功能和行为，后代事实上，母体感染一些病毒与下列疾病的发生有关：情绪障碍和/或精神病的后代，这些协会是加强在后代与精神疾病的遗传风险因素。寨卡病毒（Zika virus，ZIKV）是近年来发现的一种新型病毒被鉴定为早期感染后严重神经发育综合征的病原体，怀孕的各个阶段。然而，在妊娠晚期母体ZIKV感染的影响尚未被证实。充分解决，孕产妇ZIKV感染对儿童心理健康的潜在影响也没有得到充分解决发育正常的后代进行了研究。在这里，我们建议使用小鼠模型的晚期母体ZIKV感染以表征母体-胎儿界面处的神经免疫信号传导。研究为了评估这种信号传导的后果，我们还将评估晚期母体ZIKV感染对新生儿的影响。运动、认知和社会领域行为异常的发展是精神病学的基础疾病（例如，自闭症、精神分裂症）。最后，我们将使用已建立的人类22q11.2小鼠模型缺失综合征，一种常见的精神疾病遗传易感因素，以检查相互作用效应母亲ZIKV感染与行为异常的遗传风险。这些研究将建立晚期ZIKV感染的潜在病理行为后果，为未来的研究提供信息，监测受这种全球新出现的病原体影响的个人的工作。