Maternal milk cytokines activate cognate receptors in the neonatal esophagus to program adult social behavior

母乳细胞因子激活新生儿食道中的同源受体以编程成人社会行为

基本信息

批准号：
10727420
负责人：
Miklos Toth
金额：
$ 46.34万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-13 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10727420
关键词：
Adult Adult Children Anti-Bacterial Agents Behavior Behavioral Brain Breast Feeding CCL2 gene CCL7 gene CXCL1 gene CXCL10 gene CXCL2 gene CXCR3 gene Cell Communication Cells Cognitive Cytokine Receptors Cytokine Signaling Data Development Digestion Disease Drops Duodenum Emotional Environment Epithelial Cells Epithelium Esophagus Food Generations Goals Health Hippocampus Homeostasis Human Milk Immune Immune system Immunity Immunoglobulins Infant Infant formula Infection Intestines LIF gene Liquid substance Long-Term Effects Mediating Metabolic Milk Mothers Mus Nature Neonatal Nerve Endings Nutrient Oral cavity Organ Pattern Physical activity Premature Infant Proliferating Recombinants Reporting Role Signal Induction Signal Transduction Social Adjustment Social Behavior Social Dominance Specific qualifier value Stomach Stress TNF gene Time Tissues Work chemokine cognitive development cytokine experimental study fetal programming follow-up gastrointestinal health of the mother improved in vivo innovation leukemia inhibitory factor receptor maternal condition mental development neonate next generation offspring postnatal postnatal period preclinical study programs receptor receptor expression reproductive fitness response social influence spatial memory trait

项目摘要

Breast milk is superior to baby formula because, in addition to nutrients, it also contains immunoglobulins and antibacterial substances. Milk has many additional biologically active substances, including cytokines/chemokines, but their role in infant physical, mental, and cognitive development is not known. We reported that maternal physical activity during the postnatal period reduces the level of three cytokines/chemokines, LIF, CXCL1 and CXCL2, in milk that, in turn, increases the social dominance and reproductive fitness of the offspring. More recently, we identified the cognate receptors of these cytokines in the epithelioid layer of the neonatal esophagus, a localization that may explain the behavioral effect of the otherwise labile milk cytokines, especially in the digestive environment of the lower GI track. We propose experiments to determine how maternal milk cytokines reach and interact with their target cells/receptors in the neonatal GI track and signal to alter brain development and adult offspring behavior. The significance of the proposed work is that it will specify how the neonatal esophagus, an organ not known for its functional connection to the developing brain, can sense milk borne maternal cytokines and signal to the brain to alter its development and adult social behavior.

母乳优于婴儿配方奶，因为除营养外，它还含有免疫球蛋白和抗菌物质。牛奶还有许多额外的生物活性物质，包括细胞因子/趋化因子，但它们在婴儿身体，心理和认知中的作用发展尚不清楚。我们报道了产后期间母亲的体育锻炼在牛奶中降低了三种细胞因子/趋化因子，LIF，CXCL1和CXCL2的水平增加了后代的社会优势和生殖健康。最近，我们鉴定出这些细胞因子的同源受体在新生儿的上皮层中食道，一种可以解释否则不稳定牛奶的行为效应的定位细胞因子，尤其是在下部GI轨道的消化环境中。我们提出了实验确定母牛奶细胞因子如何到达并与其靶细胞/受体相互作用新生儿GI轨迹和信号改变了大脑发育和成人后代行为。这拟议工作的意义在于，它将指定新生儿食管，不是器官以其与发育大脑的功能连接而闻名细胞因子并向大脑发出信号，以改变其发展和成人社会行为。