A New Model of Gestational Cannabis Exposure
妊娠期大麻暴露的新模式
基本信息
- 批准号:10202140
- 负责人:
- 金额:$ 23.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-15 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AgeAnimal ModelAnimalsApplications GrantsBrainBreast FeedingCNR1 geneCannabisCellsCharacteristicsConsumptionControl GroupsDevelopmentElectrophysiology (science)EndocannabinoidsEventExposure toFerretsFetal Alcohol Spectrum DisorderGoalsGrowthHumanImpairmentIndividualInterventionMapsMarijuanaMental HealthModelingMolecularMothersNational Institute of Drug AbuseNeuronal PlasticityNeuronsOcular DominancePharmaceutical PreparationsPharmacologyPregnancyProbabilityProcessProtocols documentationSignal TransductionSynapsesTHC exposureTestingThird Pregnancy TrimesterTimeVisual Cortexalcohol exposurebaseexperimental groupexperimental studyfetal marijuana exposuregamma-Aminobutyric Acidhuman modelin vivointerestmarijuana usemarijuana use in pregnancyneurobehavioralneuronal circuitryneurotransmissionnoveloffspringoptical imagingorientation selectivitypatch clamppostnatalpreventpublic health researchsensory cortexsynaptogenesistooltransmission process
项目摘要
Summary
The use of cannabis during pregnancy have dramatically increased during the last ten years.
While the effects of cannabis and its components on brain development are poorly known,
recent studies have observed frequent mental health problems in the offspring of mothers that
used marijuana during gestation. During the third trimester of human gestation the brain
undergoes a “growth spurt” that is characterized by an intensive process of synaptogenesis.
This stage is followed by a period of refinement by activity-dependent neuronal plasticity where
synapses reaching “correct targets” are strengthened whereas synapses reaching “incorrect
targets” are pruned. The exposure to drugs and certain medications during this period have the
potential to alter these processes, resulting in multiple neurobehavioral problems. It has been
demonstrated in humans and animal models that developmental THC exposure reduces the
expression of CB1r. In layer 2/3 of the visual cortex endocannabinoid neurotransmission is
essential for the expression of iLTD and for the developmental transition between high to low
GABA release probability characteristic of mature inhibitory cells in this region. Proper levels of
inhibition are essential for the ocular dominance plasticity and the establishment of neuronal
circuits responsible for neuronal orientation tuning and formation of orientation selectivity
columns. Based on this scientific premise we hypothesize that THC exposure during the third
trimester equivalent of human gestation leads to persistent reduction in endocannabinoid
transmission, resulting in an impairment in iLTD and preventing maturation of inhibition. As a
consequence, both ocular dominance plasticity and orientation selectivity would be impaired.
Here we will use a combination of in vivo and ex vivo electrophysiology and optical imaging of
intrinsic signals to test this hypothesis. The accomplishment of these experiments would result
in the development of a novel model of prenatal exposure to cannabis that could be used to
investigate mechanisms of action of gestational marijuana and potential interventions.
概括
在过去十年中,怀孕期间吸食大麻的情况急剧增加。
虽然大麻及其成分对大脑发育的影响鲜为人知,
最近的研究发现,母亲的后代经常出现心理健康问题
在怀孕期间吸食大麻。在人类妊娠晚期,大脑
经历一个“生长突增”,其特征是突触发生的密集过程。
此阶段之后是一段由活动依赖性神经元可塑性细化的时期,其中
达到“正确目标”的突触得到加强,而达到“不正确目标”的突触得到加强
“目标”被修剪。在此期间接触药物和某些药物有
改变这些过程的潜力,导致多种神经行为问题。它一直
在人类和动物模型中证明,发育时期的 THC 暴露会降低
CB1r 的表达。在视觉皮层 2/3 层,内源性大麻素神经传递是
对于 iLTD 的表达以及从高到低的发育过渡至关重要
该区域成熟抑制细胞的 GABA 释放概率特征。适当的水平
抑制对于眼部优势可塑性和神经元的建立至关重要
负责神经元方向调整和方向选择性形成的电路
列。基于这个科学前提,我们假设第三次接触 THC
相当于人类妊娠的三个月导致内源性大麻素持续减少
传输,导致 iLTD 受损并阻止抑制成熟。作为一个
结果,眼部优势可塑性和方向选择性都会受到损害。
在这里,我们将结合体内和离体电生理学和光学成像
检验这一假设的内在信号。这些实验的完成将导致
开发一种产前接触大麻的新模型,可用于
研究妊娠大麻的作用机制和潜在的干预措施。
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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Alexandre Esteves Medina其他文献
Alexandre Esteves Medina的其他文献
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{{ truncateString('Alexandre Esteves Medina', 18)}}的其他基金
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- 批准号:
10644999 - 财政年份:2022
- 资助金额:
$ 23.18万 - 项目类别:
A novel animal model to study the association between alcohol abuse during late adolescence with common conditions observed in combat Veterans
一种新的动物模型,用于研究青春期后期酗酒与退伍军人中观察到的常见状况之间的关联
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10368295 - 财政年份:2022
- 资助金额:
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Improving Neuronal Plasticity in a Mouse Model of FASD
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- 批准号:
8798554 - 财政年份:2014
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
酒精在新皮质发育和可塑性中的作用
- 批准号:
9926203 - 财政年份:2001
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
酒精在新皮质发育和可塑性中的作用
- 批准号:
8583074 - 财政年份:2001
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
酒精在新皮质发育和可塑性中的作用
- 批准号:
8461671 - 财政年份:2001
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
酒精在新皮质发育和可塑性中的作用
- 批准号:
7887815 - 财政年份:2001
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
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- 批准号:
7036983 - 财政年份:2001
- 资助金额:
$ 23.18万 - 项目类别:
Alcohol in Neocortex Development and Plasticity
酒精在新皮质发育和可塑性中的作用
- 批准号:
8660249 - 财政年份:2001
- 资助金额:
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