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Individual Variation in Effects of Traumatic Stress on Gray Matter Myelin

创伤应激对灰质髓磷脂影响的个体差异

基本信息

批准号：
9902081
负责人：
Daniela KAUFER
金额：
$ 3.28万
依托单位：
NORTHERN CALIFORNIA INSTITUTE/RES/EDU
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：
2019-01-11 至 2023-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902081
关键词：
Acute Adult Affect Amygdaloid structure Animal Model Animals Anterior Area Behavior Brain Brain imaging Confounding Factors (Epidemiology)Data Development Dorsal Exposure to Fright Functional Magnetic Resonance Imaging Hippocampus (Brain)Human Image Insula of Reil Learning Life Measures Mediator of activation protein Modeling Myelin Neuronal Plasticity Oligodendroglia Pattern Post-Traumatic Stress Disorders Prefrontal Cortex Psychometrics Rattus Research Research Domain Criteria Rodent Role Secondary to Severities Stress Structure Symptoms Synapses Testing Trauma Viral Virus axonal sprouting behavior measurement behavioral response brain abnormalities density dentate gyrus design emerging adult environmental stressor experience exposed human population fear memory gray matter human model human subject improved individual variation innovation myelination novel overexpression response translational model trauma exposure

项目摘要

PROJECT SUMMARY/ABSTRACT This research will examine maladaptive myelination as a potential mechanism underpinning the structural and functional brain abnormalities associated with exposure to traumatic stress. Specifically, we will explore the mechanisms behind persistent sensitivity to acute threat (“fear”: RDoC domain) arising from traumatic stress during early adulthood. Myelination most likely evolved to improve conduction velocity but in gray matter (GM), it reduces axonal sprouting, synaptic density, and neuroplasticity. Exciting recent findings have shown that myelin development in both cortical and subcortical gray matter is highly plastic and strongly influenced by new experiences and learning, even during adult life. Importantly, myelin-forming oligodendrocytes are sensitive to environmental stressors and therefore may provide a novel mechanism by which aberrant structural and functional changes arise in the brain. Human brain imaging data from our labs show that subjects with a range of PTSD symptoms secondary to adult trauma exposure have increased myelin content in the hippocampal (HP), frontal, and temporal GM. Importantly, myelin content predicted symptom severity over and above potential confounding variables. Furthermore, we found that adult traumatic stress exposure in rodents produces an increase in oligodendrocytes (OGs) and myelin content in the dentate gyrus (DG), a GM structure. Similar to human subjects, our preliminary data show that symptom severity (fear score) in rats is significantly correlated with DG OGs and myelin content. Overall, these findings provide a translational model to better understand the mechanisms of oligodendrocyte and myelin plasticity in the human. In this proposal, we will test the hypothesis that traumatic stress exposure during adulthood leads to increased myelination in cortical and subcortical GM in regions critical for fear memory. Specifically, we expect to see this increased myelination only in those that subsequently become sensitive to acute threat following stress exposure. Additionally, we hypothesize that increased myelination will constrain the proper functioning of the major intrinsic functional connectivity (IFC) networks. This integrated animal-human design enables an innovative multilevel and causal exploration. Additionally, we focus on a novel role for myelin plasticity in the adult brain as a mediator of trauma-induced acute threat symptoms. Aim 1 is focused on the question of whether hippocampal gray matter myelination predict post-trauma sensitivity to acute threat. Aim 2 is focused on the question of whether the effects of trauma exposure on cortical and subcortical GM myelination predict network connectivity and fear memory.

项目总结/文摘