Sex and circuit-specific determinants of exercise-induced stress resilience
运动引起的压力恢复能力的性别和循环特定决定因素
基本信息
- 批准号:10650862
- 负责人:
- 金额:$ 54.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-21 至 2027-03-31
- 项目状态:未结题
- 来源:
- 关键词:AccelerationAddressAnxietyAnxiety DisordersAutomobile DrivingBehaviorBehavioralBrainChemosensitizationChronicCommunicationCorpus striatum structureDataDesire for foodDevelopmentDiseaseDopamineDopamine D1 ReceptorExerciseFemaleFluorescent in Situ HybridizationFutureGenesGeneticGoalsKnowledgeLinkMaintenanceMediatingMental DepressionMental HealthMolecularMood DisordersMotivationMotorNeuronsOrganOutcomePeriodicityPeripheralPhasePositioning AttributePredispositionPrefrontal CortexProcessPropertyRattusResistanceRoleRunningScanningSensorimotor functionsSerotoninSex DifferencesSignal TransductionStimulusStressSubstantia nigra structureSystemTestingTimeTraumaWomanbehavioral outcomedorsal raphe nucleusemotion regulationexperienceexperimental studygenetic approachmalemenneuralneural circuitnoveloptogeneticspreventreceptor expressionrecruitrelease factorresilienceresistance exerciseresponsesedentarysensorimotor systemsexstress managementstress resiliencetreadmill trainingtreatment strategy
项目摘要
Project Summary
Women are more susceptible than are men to stress-related mood and anxiety disorders, underscoring the
importance of identifying strategies to promote stress resistance in women. Exercise affords broad benefits to
mental health in both sexes, but whether the degree of stress protection and underlying mechanisms differ
between sexes is unknown. We recently discovered that female rats are more responsive to the stress-buffering
effects of exercise than males. It takes voluntary wheel running (WVR) half the time to enable protection against
the depression- and anxiety-like effects of inescapable stress (IS) in female rats (3 wk) than it does in males (6
wk). Enhanced stress protection from exercise in females is an entirely unexplored resilience phenomenon. The
goal of this proposal is to examine the sex- and circuit-specific determinants of this process across multiple units
of analysis (molecular, cellular, circuits, sex, and behavior). VWR prevents the behavioral sequelae of IS by
constraining activation of serotoninergic (5HT) neurons in the dorsal raphe nucleus (DRN) during IS, but the
mechanism by which exercise constrains DRN 5HT activity is unknown. Our preliminary data provide strong
evidence that stress resistance in both sexes arises from engagement of sensorimotor circuits (dorsolateral
striatum; DLS) responsible for maintaining exercise. We have found that the DLS is positioned to inhibit DRN
5HT neurons through a direct GABAergic projection (DLS-DRN circuit), and 6 wk of VWR potentiates the activity
of the DLS-DRN circuit during IS. Importantly, although the DLS is required to maintain VWR behavior in both
sexes, the DLS governs VWR earlier in females (4 d) than in males (4 wk). Dopamine (DA) in the DLS contributes
to DLS-dependent behavior and females are known to have heightened stimulus-evoked dopamine (DA)
responses compared to males. This is likely the case with VWR, as just a few bouts of VWR activates D1
receptor-expressing neurons in the DLS of females, but not males. The rapid recruitment of the DLS during VWR
in females could accelerate plasticity in the DLS-DRN circuit required for constraining stress-induced 5HT
activity. Indeed, stress resistance from 3 wk of VWR in females depends on activity of the DLS-DRN circuit
during IS. These data suggest that once exercise becomes governed by the DLS, the DLS-DRN circuit now
responds actively to future adversity, thereby inhibiting the DRN & enabling stress resistance. We hypothesize
that DLS neural ensembles link exercise to stress resistance and are particularly responsive to exercise in
females, due to heightened DA responses to exercise in females compared to males. Intersectional genetic
approaches that tag, record, and manipulate neural circuit activity during initial exercise and later stress will be
used to 1) identify the role of the DLS in the development of exercise-induced stress resistance and accelerated
stress resistance in females, 2) determine the role of the DLS in the expression of exercise-induced stress
resistance in both sexes, and 3) identify the role of DA in driving accelerated stress resistance from VWR in
females and in determining whether an appetitive, sensorimotor experience enables stress resistance.
项目摘要
女性比男性更容易患上与压力有关的情绪和焦虑症,这突出了
确定提高妇女抗压能力的战略的重要性。运动对人有广泛的好处,
心理健康在两种性别,但是否压力保护程度和潜在的机制不同
性别差异是未知的。我们最近发现,雌性大鼠对压力缓冲的反应更敏感,
锻炼的效果比男性好。它需要一半的时间自愿车轮运行(WVR),以实现保护,
雌性大鼠(3周)不可避免的压力(IS)对抑郁和焦虑的影响比雄性大鼠(6周)大
wk)。女性在运动中增强的压力保护是一种完全未被探索的弹性现象。的
本提案的目标是跨多个单元检查此过程的性别和电路特定决定因素
分析(分子、细胞、电路、性别和行为)。VWR通过以下方式预防IS的行为后遗症:
抑制了IS时中缝背核(DRN)内5-HT能神经元的激活,但
运动抑制DRN 5 HT活性的机制尚不清楚。我们的初步数据显示
有证据表明,两性的压力抵抗力来自感觉运动回路(背外侧)的参与,
负责维持运动的纹状体。我们已经发现DLS的定位可以抑制DRN
5 HT神经元通过直接GABA能投射(DLS-DRN回路),6 wk的VWR加强了活动
在IS期间的DLS-DRN电路。重要的是,尽管DLS需要在两种情况下保持VWR行为,
雌性DLS支配VWR的时间(4d)早于雄性(4 wk)。DLS中的多巴胺(DA)
对DLS依赖性行为和女性是众所周知的有较高的刺激诱发多巴胺(DA)
与男性相比。VWR很可能就是这种情况,因为只有几次VWR会激活D1
受体表达神经元在DLS的女性,但不是男性。VWR期间DLS的快速募集
在女性中,可以加速限制应激诱导的5 HT所需的DLS-DRN回路的可塑性
活动事实上,雌性动物3周VWR的应激抵抗力取决于DLS-DRN回路的活性
在IS期间。这些数据表明,一旦运动成为由DLS,DLS-DRN电路现在
积极应对未来的逆境,从而抑制DRN并使其能够抵抗压力。我们假设
DLS神经系统将运动与抗压力联系起来,并且对运动特别敏感,
女性,由于提高DA反应的女性运动相比,男性。交叉遗传
在最初的锻炼和后来的压力中标记、记录和操纵神经回路活动的方法将被
用于1)确定DLS在运动诱导的应激抵抗力发展中的作用,
2)确定DLS在运动诱导的应激表达中的作用
3)确定DA在驱动VWR加速应激抗性中的作用,
女性,并在确定是否食欲,感觉运动的经验,使压力抵抗力。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
BEN N GREENWOOD其他文献
BEN N GREENWOOD的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('BEN N GREENWOOD', 18)}}的其他基金
Sex and circuit-specific determinants of exercise-induced stress resilience
运动引起的压力恢复能力的性别和循环特定决定因素
- 批准号:
10446219 - 财政年份:2022
- 资助金额:
$ 54.93万 - 项目类别:
Exercise Prevents Stress-Induced Memory Impairments
运动可以预防压力引起的记忆障碍
- 批准号:
7893385 - 财政年份:2010
- 资助金额:
$ 54.93万 - 项目类别:
Exercise Prevents Stress-Induced Memory Impairments
运动可以预防压力引起的记忆障碍
- 批准号:
8041080 - 财政年份:2010
- 资助金额:
$ 54.93万 - 项目类别:
Stress, exercise & depression: Neurochemical Mechanisms
压力、锻炼
- 批准号:
6486941 - 财政年份:2002
- 资助金额:
$ 54.93万 - 项目类别:
Stress, exercise & depression: Neurochemical Mechanisms
压力、锻炼
- 批准号:
6721255 - 财政年份:2002
- 资助金额:
$ 54.93万 - 项目类别:
Stress, exercise & depression: Neurochemical Mechanisms
压力、锻炼
- 批准号:
6626129 - 财政年份:2002
- 资助金额:
$ 54.93万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 54.93万 - 项目类别:
Research Grant