Stress-induced neuroinflammatory priming: Glucocorticoids, inflammasomes, alarmins

压力诱导的神经炎症启动：糖皮质激素、炎症小体、警报素

基本信息

批准号：
9900867
负责人：
STEVEN F MAIER
金额：
$ 37.54万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-16 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9900867
关键词：
Acute Adaptor Signaling Protein Behavioral Brain CASP1 gene Cells Chronic Chronic stress Cleaved cell Corticosterone Development Disease Etiology Exposure to Gene Proteins Genetic Transcription Glucocorticoids Goals HMGB Proteins HMGB1 gene Immune Infection Inflammasome Inflammation Inflammatory Injury Interleukin-1 beta Lead Ligation Mediating Mediator of activation protein Mental disorders Messenger RNA Microglia Multiprotein Complexes Natural Immunity Organism Peripheral Physiological Play Process Production Proteins Reaction Research Role Signal Transduction Stimulus Stress TLR2 gene Toll-like receptors autocrine behavioral response behavioral sensitization chemokine comorbidity cytokine experience immune activation in vivo neuroinflammation new therapeutic target novel paracrine pathogen prevent public health relevance receptor response sensor stressor targeted treatment

项目摘要

DESCRIPTION (provided by applicant): Neuroinflammation is now regarded to be a contributing factor in the etiology of a wide range of psychiatric disorders and a potential mediator of the extensive co-morbidities that are present between these disorders. It has been suggested that psychiatric disorders may result when "normal" neuroinflammatory responses to stimuli that induce these responses become exaggerated. The experience of both acute and more chronic stressors also are associated with the development of a number of disorders. It has been tempting to suppose that these two processes are related, but neither acute nor chronic stress have proved to produce persistent neuroinflammation beyond the stressor exposure. However, we have recently found that both acute and chronic stressors, even though they do not produce either large or long-lasting neuroinflammation, potently exaggerate neuroinflammatory responses to both peripheral and central inflammatory stimuli that are administered later. Importantly, this sensitized neuroinflammatory reaction persists for many days after stressor exposure. However, the mechanisms that lead stressors to sensitize subsequent neuroinflammation remain largely unknown. Within the past decade there has been a revolution in understanding the mechanisms involved in mediating peripheral innate immunity/inflammation. These new mechanisms and processes have been studied almost exclusively in the periphery, and whether or not they occur in the CNS is unknown. Our Preliminary Studies strongly encourage the possibility that these are present in CNS innate immune cells (microglia) and that they are involved in mediating stress-induced sensitization of neuroinflammatory responses to subsequent inflammatory challenges. The global goals of the proposed research are to a) firmly establish the presence of these processes, heretofore unstudied in brain, in brain, and b) explore the role of these processes in stress- induced sensitization of neuroinflammation, as well as the behavioral changes that typically induced by the activation of innate immune cells in the brain.

描述（由适用提供）：神经炎症现在被认为是多种精神疾病的病因的一个因素，是这些疾病之间存在的广泛合并症的潜在介体。有人提出，当诱导这些反应的刺激“正常”神经炎症反应被夸大时，可能会导致精神疾病。急性和更多慢性特征的经验也与多种疾病的发展有关。人们很想假设这两个过程是相关的，但是均未提供急性或慢性应激以产生持续的神经炎症，超出了压力源的暴露。但是，我们最近发现，即使急性压力源都不产生大型或持久的神经炎症，但后来对外围和中央炎症性刺激的神经炎症反应有可能夸大神经炎症反应。重要的是，这种敏感的神经炎症反应在压力暴露后持续了很多天。然而，导致应激源引起敏感的随后神经炎症的机制在很大程度上尚不清楚。在过去的十年中，了解介导周围先天免疫/炎症所涉及的机制有一场革命。这些新的机制和过程几乎完全在外围研究，以及它们是否出现在中枢神经系统中是未知的。我们的初步研究强烈鼓励它们存在于中枢神经系统先天免疫细胞（小胶质细胞）中的可能性，并且它们参与了介导压力诱导的神经炎性反应对随后炎症挑战的敏感性。拟议研究的全球目标是a）首先确定这些过程的存在，迄今在大脑中未被研究，b）探索这些过程在胁迫引起的神经炎症的敏感性中的作用，以及通常由大脑中先天免疫细胞激活引起的行为变化。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Acute stress induces chronic neuroinflammatory, microglial and behavioral priming: A role for potentiated NLRP3 inflammasome activation.

DOI：
10.1016/j.bbi.2020.05.063
发表时间：
2020-10
期刊：
Brain, behavior, and immunity
影响因子：
0
作者：
Frank MG;Fonken LK;Watkins LR;Maier SF
通讯作者：
Maier SF

Stress-induced neuroinflammatory priming: A liability factor in the etiology of psychiatric disorders.

DOI：
10.1016/j.ynstr.2015.12.004
发表时间：
2016-10
期刊：
NEUROBIOLOGY OF STRESS
影响因子：
5
作者：
Frank, Matthew G;Weber, Michael D;Watkins, Linda R;Maier, Steven F
通讯作者：
Maier, Steven F

Exploring the immunogenic properties of SARS-CoV-2 structural proteins: PAMP:TLR signaling in the mediation of the neuroinflammatory and neurologic sequelae of COVID-19.

DOI：
10.1016/j.bbi.2023.04.009
发表时间：
2023-07
期刊：
Brain, behavior, and immunity
影响因子：
0
作者：
通讯作者：

Acute stress induces the rapid and transient induction of caspase-1, gasdermin D and release of constitutive IL-1β protein in dorsal hippocampus.

DOI：
10.1016/j.bbi.2020.07.042
发表时间：
2020-11
期刊：
Brain, behavior, and immunity
影响因子：
0
作者：
Frank MG;Baratta MV;Zhang K;Fallon IP;Pearson MA;Liu G;Hutchinson MR;Watkins LR;Goldys EM;Maier SF
通讯作者：
Maier SF

SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: Evidence of PAMP-like properties.

DOI：
10.1016/j.bbi.2021.12.007
发表时间：
2022-03
期刊：
Brain, behavior, and immunity
影响因子：
0
作者：
Frank MG;Nguyen KH;Ball JB;Hopkins S;Kelley T;Baratta MV;Fleshner M;Maier SF
通讯作者：
Maier SF