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Sex-dependent microglial colonization and vulnerability to a neonatal infection

性别依赖性小胶质细胞定植和新生儿感染的脆弱性

基本信息

批准号：
8638122
负责人：
Jaclyn Marie Schwarz
金额：
$ 27.23万
依托单位：
UNIVERSITY OF DELAWARE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8638122
关键词：
Adolescent Amygdaloid structure Attention deficit hyperactivity disorder Autistic Disorder Bacterial Infections Behavior Birth Brain Brain Diseases Brain region CCL20 gene CCL4 gene Cerebral Palsy Cognition Cognitive Cognitive deficits Data Development Diagnosis Disease Dyslexia Embryo Emotions Employee Strikes Epidemiology Escherichia coli Infections Etiology Exhibits Female Functional disorder Goals Hippocampus (Brain)Homeostasis Human Immune Immune response Immune system Impaired cognition Infection Infiltration Injury Learning Learning Disabilities Ligands Link Maintenance Memory Mental Health Microglia Morphology Neonatal Neurodevelopmental Disorder Neurons Newborn Infant Outcome Pattern Perinatal Perinatal Infection Peripheral Physiology Process Rattus Risk Role Schizophrenia Sex Bias Sex Characteristics Shapes Source Surveys System Testing Testosterone Yolk Sac brain cell chemokine cytokine design injury and repair male neurodevelopment novel postnatal public health relevance receptor relating to nervous system research study response sex

项目摘要

Project Summary. Microglia are the resident immune cells of the brain. They are involved in many processes of brain development, the maintenance of the neural homeostasis, as well as the response to infection or injury, and repair. We have recently found a striking sex difference in the number of microglia in the developing rat brain. On postnatal day (P) 4 neonatal male rats have significantly more microglia than females in the hippocampus, cortex, and amygdala -- brain regions critical for emotion and cognition. At birth, P0, males have significantly elevated levels of two chemokines (chemotactic cytokines), CCL20 and CCL4, within the hippocampus and cortex than females. Given these data, the purpose of the present proposal is to test two interrelated hypotheses: (1) Neonatal testosterone increases the colonization of microglia in the developing male brain via the elevated expression of CCL20 and CCL4, and (2) Increased numbers of microglia within the developing male brain increases the vulnerability of males to the effects of a neonatal infection when compared to females. These data are consistent with epidemiological data that indicate males are more likely to be diagnosed with certain neurodevelopmental disorders that also have known or suspected immune etiologies, including autism, ADHD, schizophrenia, and cerebral palsy. Thus the proposed experiments will explore an important mental health issue from a novel perspective by identifying the interaction between microglial colonization of the developing brain in males and females, and the sex-dependent vulnerability of males to developmental/cognitive brain disorders.

项目摘要。小胶质细胞是大脑的常驻免疫细胞。它们参与大脑的许多过程发育，维持神经稳态，以及对感染或损伤的反应，和修复.我们最近发现，在发育中的大鼠大脑中，小胶质细胞的数量存在显著的性别差异。在出生后第4天（P），新生雄性大鼠海马中的小胶质细胞显著多于雌性大鼠，大脑皮层和杏仁核--这些区域对情绪和认知至关重要。在出生时，P0，男性有显着海马内两种趋化因子（趋化细胞因子）CCL 20和CCL 4水平升高，皮质比女性。鉴于这些数据，本提案的目的是测试两个相互关联的假设：（1）新生儿睾酮增加了发育中的男性大脑中小胶质细胞的定植， CCL 20和CCL 4的表达升高，以及（2）发育中的小胶质细胞数量增加男性大脑增加了男性对新生儿感染影响的脆弱性，女性这些数据与流行病学数据一致，表明男性更有可能被被诊断患有某些神经发育障碍，这些神经发育障碍也具有已知或疑似的免疫病因，包括自闭症多动症精神分裂症和脑瘫因此，拟议的实验将探索一个通过识别小胶质细胞之间的相互作用，在男性和女性大脑发育中的殖民化，以及男性对性别依赖的脆弱性，发育/认知脑障碍。