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Explore the gut-immune-brain axis mechanisms underlying perinatal penicillin exposure-induced sensory processing defects

探索围产期青霉素暴露引起的感觉处理缺陷的肠道-免疫-大脑轴机制

基本信息

批准号：
10260402
负责人：
Yi Zuo
金额：
$ 19.25万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA CRUZ
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-10 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10260402
关键词：
Acoustics Adolescent Adult Adverse effects Affect Antibiotics Archaea Bacteria Behavior Behavioral Brain Caring Cells Child Childhood Clinical Medicine Cognitive Communities Constitution DNA sequencing Data Defect Dendritic Spines Development Diet Discrimination Drug Exposure Exhibits Exposure to Functional disorder Gastrointestinal tract structure Health Homeostasis Human Image Immune Immune system Immunohistochemistry Life Light Link Lipopolysaccharides Literature Measures Mental disorders Microglia Morphology Mus Nerve Degeneration Neuraxis Neurocognitive Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Outcome Pattern Penicillins Perinatal Physiological Play Pregnancy Preventive measure Probiotics Process Public Health Reflex action Ribosomal DNA Risk Role Sampling Sensory Site Somatosensory Cortex Structure Synapses Testing Texture Therapeutic United States Vertebral column Vibrissae Work barrel cortex cell motility density dysbiosis early life exposure excitatory neuron experimental study fecal transplantation fungus gut dysbiosis gut microbiota hippocampal pyramidal neuron in vivo in vivo calcium imaging insight microbiota mouse model nervous system development nervous system disorder neural circuit neurodevelopment neuronal circuitry neurophysiology pediatric patients perinatal medicine postnatal postnatal development postsynaptic prepulse inhibition prevent probiotic supplementation response sensory discrimination sensory processing disorder synaptic pruning therapeutic target

项目摘要

Project Summary The gut microbiota, a community of symbiotic bacteria, fungi, and archaea residing in the mammalian gastrointestinal tract, plays an integral role in the neurodevelopment and neurophysiology of the host. Its disruption has been associated with neurodevelopmental and neurodegenerative diseases. Microglia are the resident immune cells in the central nervous system; they are continually influenced by gut microbiota, raising the possibility that microglia dysfunction may be the link between dysbiosis and altered brain functions. This proposal investigates how early-life exposure to penicillin, the most-used antibiotics in perinatal medicine, affects the interplay between gut microbiota, the immune system, cortical development, and sensory processing in mice, and explores the potential of probiotics as a preventative measure. Aim 1 studies how perinatal penicillin exposure (PPE)-induced gut dysbiosis affects cortical microglia and sensory processing in adolescent and adult mice. It also explores whether early postnatal normalization of gut microbiota prevents microglia activation and behavioral defects later in life. Aim 2 studies how PPE alters microglia motility, their synaptic contact, synapse pruning, and cortical neuronal activities associated with the defective sensory processing. This study will advance our understanding of the gut-immune-brain axis in neural development, circuit function, and behavior, with significant relevance to clinical medicine and public health.

项目摘要肠道微生物群是哺乳动物体内的共生细菌、真菌和古菌群落，在宿主的神经发育和神经生理学中起着不可或缺的作用。其破坏与神经发育和神经变性疾病有关。小胶质细胞是中枢神经系统中的常驻免疫细胞;它们不断受到肠道微生物群的影响，小胶质细胞功能障碍可能是生态失调和脑功能改变之间的联系。这该提案调查了早期生命暴露于青霉素（围产期医学中最常用的抗生素），影响肠道微生物群，免疫系统，皮质发育和感觉之间的相互作用在小鼠中进行处理，并探索益生菌作为预防措施的潜力。目标1研究如何围产期青霉素暴露（PPE）诱导的肠道生态失调影响皮质小胶质细胞和感觉加工，青春期和成年小鼠。它还探讨了出生后早期肠道微生物群的正常化是否会阻止小胶质细胞激活和行为缺陷。目的2研究PPE如何改变小胶质细胞的运动性，突触接触，突触修剪，皮层神经元活动与缺陷的感觉处理.这项研究将促进我们对神经发育中肠-免疫-脑轴的理解，电路功能和行为，与临床医学和公共卫生具有重要的相关性。