Psychological stress reduces endocannabinoid tone: mechanisms and possible treatments
心理压力降低内源性大麻素张力:机制和可能的治疗方法
基本信息
- 批准号:9452362
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-10-01 至 2022-09-30
- 项目状态:已结题
- 来源:
- 关键词:2-arachidonylglycerol2-arachidonylglycerol signalingAdrenergic AgentsAdrenergic ReceptorAffectAnimal ModelAnxietyAnxiety DisordersApplications GrantsAttenuatedBehavioralBrain regionCerebellumChronic stressDataDevelopmentEmotional StressEndocannabinoidsEnzymesExhibitsExtinction (Psychology)FDA approvedFoxesFrightGeneral PopulationGenetic TranscriptionImpairmentIndividualInterneuronsInterventionInvestigationKnowledgeLearningLifeLife ExperienceLoxP-flanked alleleMembraneMemoryMemory impairmentMental DepressionMental HealthMetabolismModelingMonoacylglycerol LipasesMood DisordersMusNeuronsNorepinephrineOdorsPainPharmaceutical PreparationsPharmacologyPhenotypePost-Traumatic Stress DisordersPotassium ChannelProductionPsychological StressPurkinje CellsReceptor SignalingRegulationResearchRodentRoleSignal PathwayStressStructure of molecular layer of cerebellar cortexSynaptic TransmissionTestingUrineVeteransanxiety-like behaviorbiological adaptation to stressconditioned feardesigner receptors exclusively activated by designer drugsendocannabinoid signalingexperienceexperimental studyfear memorygamma-Aminobutyric Acidin vivolipoprotein lipaselocus ceruleus structurememory consolidationmemory retentionneural circuitneuronal excitabilitynew therapeutic targetnovelnovel strategiesnovel therapeutic interventionpresynapticpreventpsychological traumareduce symptomsresponsestressorsynthetic enzymetransmission processtraumatic eventtreatment strategy
项目摘要
One debilitating mental health problem among veterans is post-traumatic stress disorder
(PTSD), which is an anxiety disorder (PTSD) and develops following the experience of life-
threatening psychological trauma. Individuals with PTSD have reduced circulating levels of
endocannabinoids (eCB) including 2-AG. Since disruption of 2-AG signaling leads to mood
disorders, impaired memory extinction and enhanced pain, the ability to reverse the stress-
induced change in 2-AG production/degradation holds great potential for the treatment of PTSD.
Given the importance of 2-AG signaling in the stress response and associative fear learning, an
understanding of how stress produces a lasting decrease in 2-AG levels is needed to bridge
the knowledge gap that exists between traumatic stress and the associated reduction in 2-AG
content. Exposure of rodents to natural predator odors causes psychological stress, leading to
enhanced associative fear learning and thus has been used to model several aspects of PTSD.
We have previously shown that fox urine exposure produced a lasting increase in excitatory
synaptic transmission via the activation of adrenergic receptors in the mouse cerebellum. This
brain region is required for the innate response to predator odor and for the consolidation of fear
memory. Our pilot data show that predator odor exposure reduced 2-AG signaling in the
cerebellum and this stressor abolished A-type K currents in inhibitory interneurons. Therefore
our central hypothesis is that predator odor stress enhances excitability of GABAergic
interneurons and thereby reduces 2-AG signaling, thus pharmacological interventions that
inhibit 2-AG degradation and reduce neuronal excitability would reverse the stress-induced
decrease in 2-AG levels. In Aim 1, we will determine whether a psychological stress reduces 2-
AG tone by increasing 2-AG degradation or by reducing 2-AG production. Aim 2 will test the
hypothesis that emotional stress reduces 2-AG signaling by increasing inhibitory interneuron
activity. We will test whether several FDA approved drugs that reduce neuronal activity can
reverse the stress-induced change. Because the proposed study investigates a new mechanism
underlying the regulation of 2-AG metabolism by psychological stress, it could suggest novel
treatment strategies for PTSD and new therapeutic targets.
退伍军人中一个使人衰弱的心理健康问题是创伤后应激障碍
项目成果
期刊论文数量(0)
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科研奖励数量(0)
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专利数量(0)
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Siqiong June Liu其他文献
phenotype in mouse cerebellar stellate cells channel activity alters synaptic AMPA receptor + -activated large-conductance K 2+ Inhibition of Ca
小鼠小脑星状细胞表型通道活性改变突触 AMPA 受体激活的大电导 K 2 抑制 Ca
- DOI:
- 发表时间:
2011 - 期刊:
- 影响因子:0
- 作者:
J. Savtchouk;S. Acharjee;Siqiong June Liu - 通讯作者:
Siqiong June Liu
Emotional stress increases GluA2 expression and potentiates fear memory via adenylyl cyclase 5
情绪应激通过腺苷酸环化酶 5 增加 GluA2 表达并增强恐惧记忆。
- DOI:
10.1016/j.celrep.2024.115180 - 发表时间:
2025-01-28 - 期刊:
- 影响因子:6.900
- 作者:
Qian Yang;Ahmad Abdulla;Muhammad Farooq;Yoshihiro Ishikawa;Siqiong June Liu - 通讯作者:
Siqiong June Liu
Alteration of AMPA Receptor-Mediated Synaptic Transmission by Alexa Fluor 488 and 594 in Cerebellar Stellate Cells123
Alexa Fluor 488 和 594 对小脑星状细胞中 AMPA 受体介导的突触传递的改变123
- DOI:
- 发表时间:
2016 - 期刊:
- 影响因子:3.4
- 作者:
Matthieu Maroteaux;Siqiong June Liu - 通讯作者:
Siqiong June Liu
Stellate Cells: Synaptic Processing and Plasticity
星状细胞:突触处理和可塑性
- DOI:
10.1007/978-3-319-97911-3_33-2 - 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
Siqiong June Liu;C. Dubois - 通讯作者:
C. Dubois
HippocampusSynapses in Area CA3 of the Mouse Y5 Receptors Mediate Neuropeptide Y Actions at
小鼠 Y5 受体 CA3 区的海马突触介导神经肽 Y 的作用
- DOI:
- 发表时间:
2015 - 期刊:
- 影响因子:0
- 作者:
P. A. Castro;R. Palmiter;S. Baraban;C. Dubois;P. Ramamoorthy;M. Whim;Siqiong June Liu;B. Beck;G. Pourié - 通讯作者:
G. Pourié
Siqiong June Liu的其他文献
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{{ truncateString('Siqiong June Liu', 18)}}的其他基金
Psychological stress reduces endocannabinoid tone: mechanisms and possible treatments
心理压力降低内源性大麻素张力:机制和可能的治疗方法
- 批准号:
10292952 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Psychological stress reduces endocannabinoid tone: mechanisms and possible treatments
心理压力降低内源性大麻素张力:机制和可能的治疗方法
- 批准号:
10046274 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Psychological stress reduces endocannabinoid tone: mechanisms and possible treatments
心理压力降低内源性大麻素张力:机制和可能的治疗方法
- 批准号:
10616660 - 财政年份:2018
- 资助金额:
-- - 项目类别:
Impact of stress on GluR2 transcription and learning-induced synaptic plasticity
压力对 GluR2 转录和学习诱导的突触可塑性的影响
- 批准号:
8446283 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Impact of stress on GluR2 transcription and learning-induced synaptic plasticity
压力对 GluR2 转录和学习诱导的突触可塑性的影响
- 批准号:
9027880 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Impact of stress on GluR2 transcription and learning-induced synaptic plasticity
压力对 GluR2 转录和学习诱导的突触可塑性的影响
- 批准号:
8297527 - 财政年份:2012
- 资助金额:
-- - 项目类别:
Impact of stress on GluR2 transcription and learning-induced synaptic plasticity
压力对 GluR2 转录和学习诱导的突触可塑性的影响
- 批准号:
8826180 - 财政年份:2012
- 资助金额:
-- - 项目类别:














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