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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：
10435579
负责人：
Brian Daniels
金额：
$ 18.64万
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 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10435579
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.

摘要大量证据表明，病毒感染后的母体免疫激活是一种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，可以在其他发育正常的情况下接触胎儿组织并永久改变大脑功能和行为后代。事实上，母体感染多种病毒与婴儿的发病有关。子代的情绪障碍和/或精神病，这些联系在患有先前存在的精神疾病的遗传风险因素。寨卡病毒(Zika Virus，ZIKV)是近年来出现的新病原体被确认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，孕妇在妊娠晚期感染寨卡病毒的影响尚未得到证实。母亲感染寨卡病毒对儿童心理健康的潜在影响也没有得到充分解决对发育正常的后代进行了调查。在这里，我们建议使用一种晚期的小鼠模型母体ZIKV感染以表征母胎界面的神经免疫信号。为了研究这一信号的后果，我们还将评估晚期母体ZIKV感染对作为精神病学基础的运动、认知和社会领域的行为异常的发展精神障碍(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，以检查交互作用的影响具有行为异常遗传风险的母体寨卡病毒感染。这些研究将确立晚期寨卡病毒感染的潜在病理行为后果，为未来的研究和监测受这种全球新出现的病原体影响的个人的努力。