Targets of Oxytocin Receptor Signaling

催产素受体信号传导的靶点

• 批准号: 9901580
• 负责人: MOSES VICTOR CHAO
• 金额: $ 46.79万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901580
• 关键词: Address; Affect; Antibodies; Auditory area; Auditory system; Behavior; Behavioral; Biological Assay; Brain; Brain-Derived Neurotrophic Factor; Calcium; Caring; Cells; Clinical Trials; Cognition; Coupling; Distress; Electron Microscopy; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Goals; Hippocampus (Brain); Hormones; Human; Hypothalamic structure; Image; Immunohistochemistry; Impairment; Infant; Intranasal Administration; Link; Maternal Behavior; Measures; Mediating; Mental disorders; Mites; Molecular; Mus; Nerve Growth Factor Receptors; Neurons; Neuropeptides; Neurotrophic Tyrosine Kinase Receptor Type 2; Neurotrophic Tyrosine Kinase Receptor Type 3; Noise; Outcome; Outcome Measure; Oxytocin; Oxytocin Receptor; Pathway interactions; Peripheral; Pharmacology; Physiological; Protein Tyrosine Kinase; Proteins; Proteomics; Receptor Protein-Tyrosine Kinases; Receptor Signaling; Reproduction; Retrieval; Role; Scaffolding Protein; Signal Transduction; Signal Transduction Pathway; Social Behavior; Social Interaction; Synaptic plasticity; System; Techniques; Testing; Thalamic structure; Therapeutic; Therapeutic Effect; Time; Tissues; Translating; Trust; Vasopressin Receptor; anxiety treatment; anxiety-related behavior; autism spectrum disorder; autistic children; base; behavior measurement; developmental disease; experimental study; frontal lobe; gephyrin; improved; inhibitory neuron; neuromechanism; neuronal excitability; peptide hormone; pup; receptor; release of sequestered calcium ion into cytoplasm; reproductive; response; social; social anxiety; social attachment; social cognition; social deficits; src-Family Kinases; supraoptic nucleus; synaptic inhibition; tool

Oxytocin is an evolutionary conserved peptide hormone that is synthesized and released from the hypothalamus for reproduction and maternal behavior. Recent studies have tagged oxytocin as a “trust” hormone, that promises to improve social deficits in various mental disorders, such as autism. Despite the enthusiasm for oxytocin, the efficacy of oxytocin in improving human social behaviors has been contradictory. Such inconsistencies are likely due to our poor understanding of complexity of oxytocin action and the behavioral measures that have been used in clinical trials. A better understanding of the mechanisms of oxytocin is needed to apply the therapeutic potential of this neuropeptide. Recently we showed that oxytocin enables mice to recognize infant distress calls through the auditory system that enhanced maternal pup retrieval thru oxytocin receptors. The hypothesis of this application is that the identification of downstream targets of oxytocin receptors will provide a means of analyzing oxytocin signaling across molecular, physiological, systems and behavioral levels. We have developed new assays and antibodies to follow the action of the oxytocin receptor, a G protein-coupled receptor. The aim of this project is to understand how the many actions of oxytocin are translated from its receptor signal transduction pathways. An initial goal will be to follow the downstream proteins that mediate the functions of oxytocin. This includes G proteins, calcium- dependent proteins, scaffold proteins like gephyrin and receptor tyrosine kinases, such as the BDNF TrkB receptor.

催产素是一种进化保守的多肽荷尔蒙，由 负责生殖和母性行为的下丘脑。最近的研究表明，催产素是一种 “信任”荷尔蒙，承诺改善各种精神障碍的社会缺陷，如自闭症。 尽管人们对催产素充满热情，但催产素在改善人类社会行为方面的功效 自相矛盾。这种不一致很可能是因为我们对 催产素作用和已在临床试验中使用的行为测量。更好的 需要了解催产素的机制才能应用这种药物的治疗潜力 神经肽。最近，我们发现催产素使小鼠能够识别婴儿的求救信号 通过催产素受体增强母体幼崽取回的听觉系统。的假说 这一应用是识别催产素受体的下游靶点将提供一种 在分子、生理、系统和行为水平上分析催产素信号的方法。 我们已经开发了新的分析方法和抗体来跟踪催产素受体的作用 蛋白质偶联受体。这个项目的目的是了解催产素的许多作用 是从其受体信号转导途径翻译而来的。最初的目标是遵循 调节催产素功能的下游蛋白质。这包括G蛋白，钙- 依赖蛋白、支架蛋白(如Gen)和受体酪氨酸激酶(如BDNF) TrkB受体。