Modulation of serotonin levels during development produce long-lasting changes in dopaminergic function
发育过程中血清素水平的调节会对多巴胺能功能产生持久的变化
基本信息
- 批准号:10378770
- 负责人:
- 金额:$ 40.82万
- 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:2019-04-11 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAmphetaminesAnhedoniaAnimalsAntidepressive AgentsAnxietyArousalBehaviorBehavioralBrainCellsClinicalComplexConsumptionDataDevelopmentDiseaseDopamineDopamine ReceptorDopaminergic CellDorsalDoseElectrophysiology (science)EmotionsEnvironmental Risk FactorExposure toFemaleFiberFluoxetineFutureHumanInflammationInjectionsLeadLifeMeasuresMediatingMediator of activation proteinModelingMolecularMood DisordersMoodsMotivationMusNegative ValenceNeurobiologyNeuromodulatorNeuroregulatorNucleus AccumbensOperant ConditioningOutcomePathway interactionsPharmaceutical PreparationsPharmacologic SubstancePhotometryPositive ValencePredispositionPregnancyPregnancy TrimestersPreparationProcessRegulationRewardsRodentRoleSelective Serotonin Reuptake InhibitorSerotonergic SystemSerotoninSignal TransductionSocial BehaviorSocial InteractionStressSucroseSystemTestingThird Pregnancy TrimesterTimeUmbilical Cord BloodVentral Tegmental AreaWestern BlottingWomanWorkanxiety-like behaviorapproach avoidance behaviorautism spectrum disorderbasebehavior testbehavioral impairmentcritical perioddopamine systemdopamine transporterdopaminergic neurondorsal raphe nucleusearly life exposureemotion regulationexperimental studyfetalgenetic manipulationimprovedinhibitormaladaptive behaviormalemotivated behaviorneuronal circuitryneuropsychiatric disorderoffspringoptogeneticsperinatal periodpreventpupresponsereuptakesocialwillingness
项目摘要
Project Summary
The perinatal period is marked by intense plasticity, making it vulnerable to environmental factors that can derail
normal brain development and lead to maladaptive behaviors in the adult. High levels of serotonin during
development resulting from genetic manipulations, maternal inflammation or administration of selective-
serotonin-reuptake-inhibitors (SSRIs) lead to alterations in brain development and/or to behavioral deficits in
adult rodents such as anhedonia, anxiety-like behaviors and social interaction deficits. In our preliminary work,
we have found that increasing serotonergic tone during the perinatal period leads to decreased exploration,
decreased response to an amphetamine challenge and motivation deficits. Interestingly, these behaviors are
dependent on the dopaminergic system, a known regulator of mood, reward seeking and motivated behavior.
During development, the serotonergic system develops earlier than the dopaminergic one and the Dorsal Raphe
nucleus projects strongly to the Ventral Tegmental Area, enabling the serotonergic system to modulate the
dopaminergic one. While most studies have focused on the effects of abnormal developmental serotonin levels
on the serotonergic system itself or on cortical development, how it affects the dopaminergic system and function
is unknown. We hypothesize, based on preliminary data, that high levels of serotonin during development disturb
dopaminergic function through the Dorsal Raphe > Ventral Tegmental Area > Nucleus Accumbens pathway
resulting in behavioral deficits in the adult. Using a combination of behavioral testing, optogenetics and
electrophysiology, we will assess how elevated serotonin levels during development affect our target
dopaminergic circuit. In Aim 1, we expand on our preliminary data to characterize the extent to which dopamine-
dependent behaviors are affected in mice exposed to SSRIs during the perinatal period. In Aim 2, we delineate
the molecular, cellular and circuit bases of the deficits in dopamine-dependent tasks observed in our preliminary
data. Understanding the regulation and the interactions between serotonin and dopamine in this key
monoaminergic circuit can have clinical implications spanning from mood disorders to autism and motivational
aspects of behavior. Furthermore, although our serotonergic manipulation is optimal from experimental and
neurobiological perspectives, it is also potentially relevant to real-world clinical situations. Indeed, some
pregnancies require the use of antidepressants, which typically increase fetal serotonin levels. An enhanced
understanding of the behavioral consequences and the mediating mechanisms of early elevations in
serotonergic levels may have substantial implications for improving the lifelong outcomes of the offspring of such
pregnancies in the future.
项目摘要
围产期以强烈的可塑性为标志,使其容易受到可能脱轨的环境因素的影响。
正常的大脑发育,并导致成年人的不适应行为。体内高水平的5-羟色胺
由基因操作、母体炎症或选择性-
5-羟色胺再摄取抑制物(SSRI)导致脑发育改变和/或行为缺陷
成年啮齿动物如快感缺乏、焦虑样行为和社交缺陷。在我们的前期工作中,
我们发现,围产期增加5-羟色胺能张力会导致探查活动减少,
对安非他命挑战的反应减弱,动力不足。有趣的是,这些行为
依赖于多巴胺能系统,这是一种已知的情绪、奖励寻求和动机行为的调节器。
在发育过程中,5-羟色胺能系统的发育早于多巴胺能系统和中缝背侧。
核团强烈投射到腹侧被盖区,使5-羟色胺能系统能够调节
多巴胺能一号。虽然大多数研究都集中在发育异常的5-羟色胺水平的影响上
5-羟色胺能系统本身或皮质发育,它如何影响多巴胺能系统和功能
是未知的。根据初步数据,我们推测,在发育过程中,高水平的5-羟色胺会干扰
中缝腹侧被盖区伏核通路对多巴胺能神经的作用
导致成年人的行为缺陷。使用行为测试、光遗传学和
电生理学,我们将评估在发育过程中升高的5-羟色胺水平如何影响我们的目标
多巴胺能回路。在目标1中,我们扩展了我们的初步数据,以表征多巴胺-
在围产期暴露于SSRIs的小鼠的依赖行为受到影响。在目标2中,我们描绘了
我们初步观察到的多巴胺依赖任务缺陷的分子、细胞和电路基础
数据。了解5-羟色胺和多巴胺在该钥匙中的调节和相互作用
单胺能环路可能具有从情绪障碍到自闭症和动机障碍的临床意义
行为的各个方面。此外,尽管我们的5-羟色胺能操纵是从实验和
从神经生物学的角度来看,它也可能与现实世界的临床情况相关。的确,有些人
怀孕需要使用抗抑郁药,这通常会增加胎儿的血清素水平。增强版
对早期海拔高度的行为后果及其调节机制的理解
5-羟色胺能水平可能对改善此类后代的终生结局具有重要意义
未来的怀孕情况。
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)
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 }}
Catia Teixeira其他文献
Catia Teixeira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('Catia Teixeira', 18)}}的其他基金
Role of PFC Activity in the Behavioral Deficits Induced by Maternal Separation
PFC 活性在母亲分离引起的行为缺陷中的作用
- 批准号:
10567520 - 财政年份:2023
- 资助金额:
$ 40.82万 - 项目类别:
Modulation of serotonin levels during development produce long-lasting changes in dopaminergic function
发育过程中血清素水平的调节会对多巴胺能功能产生持久的变化
- 批准号:
9913566 - 财政年份:2019
- 资助金额:
$ 40.82万 - 项目类别:
Modulation of serotonin levels during development produce long-lasting changes in dopaminergic function
发育过程中血清素水平的调节会对多巴胺能功能产生持久的变化
- 批准号:
10609846 - 财政年份:2019
- 资助金额:
$ 40.82万 - 项目类别:
相似海外基金
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
- 批准号:
BB/Z514391/1 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
- 批准号:
2312555 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
- 批准号:
2327346 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
- 批准号:
ES/Z502595/1 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
- 批准号:
23K24936 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
- 批准号:
ES/Z000149/1 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
- 批准号:
2901648 - 财政年份:2024
- 资助金额:
$ 40.82万 - 项目类别:
Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
- 批准号:
488039 - 财政年份:2023
- 资助金额:
$ 40.82万 - 项目类别:
Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
- 批准号:
23K00129 - 财政年份:2023
- 资助金额:
$ 40.82万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
- 批准号:
2883985 - 财政年份:2023
- 资助金额:
$ 40.82万 - 项目类别:
Studentship