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Impact of Neonatal Infection on the Development of Hippocampal-Dependent Learning

新生儿感染对海马依赖性学习发展的影响

基本信息

批准号：
9029616
负责人：
Jaclyn Marie Schwarz
金额：
$ 35.53万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9029616
关键词：
ARHGEF5 gene Adolescent Adult Affect Age Area Attention deficit hyperactivity disorder Autistic Disorder Behavior Brain Brain region Brain-Derived Neurotrophic Factor Cell physiology Cells Child Childhood Data Development Developmental Delay Disorders Diagnosis Disease Early Diagnosis Environmental Risk Factor Etiology Event Female Fright Future Goals High Prevalence Hippocampus (Brain)Human Immune Immune system Infection Interleukin-1 beta Intrinsic factor Language Learning Learning Disabilities Learning Skill Life Memory Microglia Minocycline Molecular Target Morphology Motor Skills Neonatal Neurons Peripheral Phenotype Rattus Research Research Personnel Risk Factors Sex Characteristics Sex Functioning Structure Stuttering Synaptic plasticity System Testing Therapeutic Intervention Time boys brain behavior design developmental disease girls immune activation immune function inhibitor/antagonist learning outcome male neural circuit neurotrophic factor postnatal public health relevance relating to nervous system research study response sex social skills theories

项目摘要

DESCRIPTION (provided by applicant): Developmental disorders are one of several disorders that interrupt normal development in childhood. These disorders may affect only one or several different areas of development, including language, motor, social and learning skills. Learning disabilities in particular are one of the most common forms of developmental disorders and are typically diagnosed early in children. Notably, learning disabilities and developmental disorders, in general, are more often diagnosed in boys than in girls and it is thought, at least in part, to e the result of immune activation during early brain development. Despite these theories, the underlying etiologies of many developmental disorders are not well understood, particularly in the context of peripheral immune function, microglial function, and sex. The purpose of the proposed experiments is two-fold. First, we will seek to understand normal hippocampal development of microglia and the developmental expression of synaptic plasticity molecules during the onset of hippocampal dependent contextual fear learning in juvenile male and female rats. Second, we will examine how activation of the developing immune system in males and females may result in subsequent delays in microglial development, the expression of synaptic plasticity molecules in the hippocampus, and developmental delays in hippocampal dependent learning in a sex-dependent manner. The results of these experiments will significantly increase our understanding of the interactions between intrinsic factors (such as sex) and environmental factors (such as immune activation) that perturb the normal development of brain and behavior from the juvenile period and into adulthood. In addition, these experiments will identify new molecular targets of neuronal and glial interactions that are likely disrupted throughout development as a result of early-life immune activation, providing potential targets for future therapeutic interventions.