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Determining astrocytic contributions to memory-related dimensions of PTSD

确定星形胶质细胞对 PTSD 记忆相关维度的贡献

基本信息

批准号：
10015350
负责人：
Brian George DIAS
金额：
$ 3.67万
依托单位：
EMORY UNIVERSITY
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：
2019-09-10 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10015350
关键词：
Adult Affect Astrocytes Behavior Behavioral Brain Brain region Cells Chemicals Corticosterone Data Data Reporting Development Dimensions Drug Targeting Event Exposure to Extinction (Psychology)FDA approved Fright Functional disorder Future Glucocorticoid Receptor Goals Hormone Receptor Hormones Impairment Knock-out Learning Light Link Measures Mediating Memory Molecular Mus Nervous system structure Neuroglia Neurons Outcome Paroxetine Pathology Pathway interactions Pharmacological Treatment Play Population Post-Traumatic Stress Disorders Prefrontal Cortex Recording of previous events Risk Factors Role Sertraline Shock Signal Pathway Signal Transduction Stimulus Stress Testing Time Training Trauma Work biological adaptation to stress cell type cellular targeting conditioned fear fear memory knock-down learning extinction neuropsychiatric disorder neurotransmission notch protein novel novel therapeutic intervention novel therapeutics post-traumatic symptoms receptor expression receptor function transcription factor translational impact traumatic event

项目摘要

PROJECT SUMMARY Post Traumatic Stress Disorder (PTSD) is a devastating neuropsychiatric disorder that develops after trauma. A previous history of stress exposure significantly increases the likelihood of developing PTSD after a traumatic event. Deficits in extinction learning are a debilitating and core symptom of PTSD. This inability to learn that stimuli previously linked to trauma are no longer threatening causes maladaptive fear expression toward these stimuli. Efforts to reduce stress-induced deficits in extinction learning have included identifying stress-induced perturbations of molecular pathways in the brain. Most of this work has either treated brain regions as a homogeneous population of cells or mainly focused on neurons. While glia are the most populous cells in the nervous system, we have little appreciation for their contribution to stress-induced deficits in extinction learning. In this proposal, we examine how molecular events in astrocytes (the most predominant glial cell population) influence stress-induced deficits in extinction learning. More specifically, we study the relationship between astrocytes in the infra-limbic prefrontal cortex, a brain region important for extinction learning and stress-induced deficits in extinction learning. We hypothesize that in the adult brain, stress- induced deficits in extinction learning are, in part, mediated by stress hormone action and increased activity of developmental signaling pathways, in astrocytes of the infra-limbic prefrontal cortex. To test this hypothesis, we will study stress-induced deficits in extinction learning after manipulating stress hormone receptor function and the activity of developmental signaling cascades in astrocytes of the infra-limbic prefrontal cortex. Successful outcomes from our work will shed new light on how molecular function in astrocytes contribute to stress-induced impairments in extinction learning. Additionally, our work has the potential to recommend new cell-type specific molecular pathways that could be targeted to mitigate a highly prevalent and debilitating memory-related dimension of PTSD.

项目总结