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

• 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
• 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

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粉的上级原因是，除了营养成分外，它还含有 免疫球蛋白和抗菌物质。牛奶具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，精神和认知方面的作用 发展尚不清楚。我们报告说，产妇在产后期间的体力活动， 降低牛奶中三种细胞因子/趋化因子LIF、CXCL 1和CXCL 2的水平，反过来， 增加了后代的社会优势和生殖适应性。最近，我们 在新生儿的上皮样层中鉴定了这些细胞因子的同源受体， 食道，这一定位可能解释了其他不稳定乳汁的行为效应 细胞因子，特别是在下消化道的消化环境中。我们提出实验 为了确定母乳中的细胞因子如何到达并与它们的靶细胞/受体相互作用， 新生儿GI跟踪和信号改变大脑发育和成年后代的行为。的 拟议工作的意义在于，它将详细说明新生儿食管，一个器官， 以其与发育中的大脑的功能联系而闻名，可以感知母乳传播的母亲 细胞因子和信号到大脑，以改变其发展和成人的社会行为。