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

项目摘要 肠道微生物区系，哺乳动物体内由共生细菌、真菌和古菌组成的群落 胃肠道在宿主的神经发育和神经生理学中起着不可或缺的作用。它的 分裂与神经发育和神经退行性疾病有关。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区系的影响， 小胶质细胞功能障碍可能是生物失调和大脑功能改变之间的联系。这 一项提案调查了早期接触青霉素的情况，青霉素是围产期医学中最常用的抗生素， 影响肠道微生物区系、免疫系统、皮质发育和感觉之间的相互作用 在小鼠身上进行处理，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)所致大鼠肠道小胶质细胞和感觉加工障碍 青春期和成年小鼠。它还探索了出生后早期肠道微生物区系的正常化是否可以防止 小胶质细胞的激活和晚年的行为缺陷。目的2研究PPE如何改变小胶质细胞的运动，他们 与感觉缺陷相关的突触接触、突触修剪和皮质神经元活动 正在处理。这项研究将促进我们对神经发育中的肠道免疫脑轴的理解， 电路功能和行为，与临床医学和公共卫生密切相关。

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.