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:
- 金额:$ 3.28万
- 依托单位:
- 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:
- 关键词:AcuteAdultAffectAmygdaloid structureAnimal ModelAnimalsAnteriorAreaBehaviorBrainBrain imagingConfounding Factors (Epidemiology)DataDevelopmentDorsalExposure toFrightFunctional Magnetic Resonance ImagingHippocampus (Brain)HumanImageInsula of ReilLearningLifeMeasuresMediator of activation proteinModelingMyelinNeuronal PlasticityOligodendrogliaPatternPost-Traumatic Stress DisordersPrefrontal CortexPsychometricsRattusResearchResearch Domain CriteriaRodentRoleSecondary toSeveritiesStressStructureSymptomsSynapsesTestingTraumaViralVirusaxonal sproutingbehavior measurementbehavioral responsebrain abnormalitiesdensitydentate gyrusdesignemerging adultenvironmental stressorexperienceexposed human populationfear memorygray matterhuman modelhuman subjectimprovedindividual variationinnovationmyelinationnoveloverexpressionresponsetranslational modeltrauma 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
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Daniela KAUFER其他文献
Daniela KAUFER的其他文献
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{{ truncateString('Daniela KAUFER', 18)}}的其他基金
Non-invasive lighting treatment as a novel therapeutic for age-related cognitive decline
非侵入性照明治疗作为治疗与年龄相关的认知衰退的新型疗法
- 批准号:
10681091 - 财政年份:2023
- 资助金额:
$ 3.28万 - 项目类别:
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
- 批准号:
10337050 - 财政年份:2019
- 资助金额:
$ 3.28万 - 项目类别:
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
- 批准号:
10516079 - 财政年份:2019
- 资助金额:
$ 3.28万 - 项目类别:
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
- 批准号:
10058275 - 财政年份:2019
- 资助金额:
$ 3.28万 - 项目类别:
Identification & Prevention of Developmental Myelin Misregulation in PTSD
鉴别
- 批准号:
8103728 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
TGF-beta Mediated Inflammatory Signaling: a critical role in epileptogenesis
TGF-β介导的炎症信号传导:在癫痫发生中的关键作用
- 批准号:
8928881 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
TGF-beta Mediated Inflammatory Signaling: a Critical Role in Epileptogenesis
TGF-β介导的炎症信号传导:在癫痫发生中的关键作用
- 批准号:
8106182 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
Identification & Prevention of Developmental Myelin Misregulation in PTSD
鉴别
- 批准号:
8096781 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
TGF-beta Mediated Inflammatory Signaling: a Critical Role in Epileptogenesis
TGF-β介导的炎症信号传导:在癫痫发生中的关键作用
- 批准号:
7792320 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
Identification & Prevention of Developmental Myelin Misregulation in PTSD
鉴别
- 批准号:
7765632 - 财政年份:2009
- 资助金额:
$ 3.28万 - 项目类别:
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