PACAP Signaling in Fear Circuitries Relevant to Post-Traumatic Stress Disorder

与创伤后应激障碍相关的恐惧回路中的 PACAP 信号传导

基本信息

批准号：
8463349
负责人：
Michael S Fanselow
金额：
$ 23.1万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-12-20 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8463349
关键词：
Affect Amygdaloid structure Anxiety Disorders Behavior Behavioral Biological Biological Markers Brain region Cell membrane Complement Corticotropin-Releasing Hormone Development Disease Drug Targeting Epigenetic Process Extinction (Psychology)Foundations Fright Gene Targeting Genes Genetic Genetic Models Heterotrimeric GTP-Binding Proteins Injection of therapeutic agent Laboratories Lead Link Mediator of activation protein Mental disorders Molecular Mus Neurons Neuropeptides PACAPR-1 protein Pathway interactions Peptide Signal Sequences Peptides Pituitary Gland Population Post-Traumatic Stress Disorders Reporting Research Personnel Risk Rodent Signal Transduction Stress Structure of terminal stria nuclei of preoptic region Symptoms Testing Translating base conditioned fear interest midbrain central gray substance novel patient population prevent public health relevance recombinase relating to nervous system research study response therapeutic target therapy design tool

项目摘要

DESCRIPTION (provided by applicant): Understanding the biological mechanisms and biomarkers of psychiatric disease is critical for understanding, assessing risk, and designing treatments of disorders such as post traumatic stress disorder (PTSD). In this regard, it was recently reported that the neuropeptide PACAP and its plasma membrane receptor PAC1 are linked to PTSD at both genetic and epigenetic levels. These findings complement a considerable set of prior evidence implicating PACAP/PAC1 signaling in stress and fear circuitries. Experiments in the proposal will use gene targeting approaches to dissect at the cellular, molecular, and behavioral levels, the involvement of PACAP-PAC1 signaling in the circuitry regulating fear in mice. The results are hoped to lay a mechanistic foundation for the development of an entirely new set of therapeutic targets for PTSD based on PAC1 signaling and downstream actions, and may also lead to the discovery of novel and robust biomarkers associated with this pathway.

描述（由申请人提供）：了解精神疾病的生物学机制和生物标志物对于理解、评估风险和设计创伤后应激障碍（PTSD）等疾病的治疗方法至关重要。在这方面，最近有报道称，神经肽 PACAP 及其质膜受体 PAC1 在遗传和表观遗传水平上与 PTSD 相关。这些发现补充了大量先前的证据，表明 PACAP/PAC1 信号传导在压力和恐惧回路中。该提案中的实验将使用基因靶向方法在细胞、分子和行为水平上剖析 PACAP-PAC1 信号传导在小鼠恐惧调节电路中的参与情况。希望这些结果能够为基于 PAC1 信号传导和下游作用的一套全新的 PTSD 治疗靶点的开发奠定机制基础，并且还可能导致与该途径相关的新颖且强大的生物标志物的发现。