Targets of Oxytocin Receptor Signaling

催产素受体信号传导的靶点

基本信息

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
项目类别：
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

项目摘要

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肽马酮，已合成并从下丘脑生殖和孕产妇行为。最近的研究已将氧气标记为 “信任”本人有望改善各种精神障碍（例如自闭症）的社会缺陷。尽管对氧气充满热情，但氧气在改善人类社会行为方面的效率还是是矛盾的。这样的不一致可能是由于我们对催产素的作用和已在临床试验中使用的行为测量。更好需要了解氧加毒素的机制以应用其治疗潜力神经肽。最近，我们表明氧加毒素使小鼠能够通过通过催产素受体提高遗传幼崽检索的听觉系统。假设该应用是识别氧受体下游靶标将提供分析分子，物理，系统和行为水平的氧信号的手段。我们开发了新的测定法和抗体，以遵循催产素受体的作用，A g 蛋白质偶联受体。该项目的目的是了解催产素的许多作用从其接收器信号翻译途径转换。最初的目标是遵循介导催产素功能的下游蛋白。这包括G蛋白，钙 - 依赖性蛋白质，脚手架蛋白（如Gephyrin和受体酪氨酸激酶），例如BDNF TRKB接收器。