In utero ethanol exposure & development of GABAergic cortical interneurons
子宫内乙醇暴露
基本信息
- 批准号:7321656
- 负责人:
- 金额:$ 4.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-12-01 至 2008-11-30
- 项目状态:已结题
- 来源:
- 关键词:AffectAgeAlcohol consumptionAppearanceBehavioralBiologicalBrainCellsChronicCoculture TechniquesComputer information processingDefectDependenceDevelopmentDietDisruptionDoseEmbryoEmbryonic DevelopmentEnvironmental Risk FactorEthanolFetal Alcohol ExposureFetal Alcohol SyndromeGenesGreen Fluorescent ProteinsHeightHydrocephalusIn VitroInterneuronsKineticsLiquid substanceMedialMicrocephalyMolecularMorphologyMutateNeocortexNumbersPatient currently pregnantPatternPopulationPositioning AttributePredispositionPregnancyRegulationRodentRunningSeizuresSensorySliceSourceStagingSystemTestingTimeTransgenic MiceVideo Microscopyalcohol consumption during pregnancyalcohol exposurechronic alcohol ingestiondayextracellularfeedinggamma-Aminobutyric Acidin uteroin vivomigrationneuronal circuitrypostnatalprenatalreceptorresearch study
项目摘要
Consumption of ethanol during pregnancy can be detrimental to the offspring, the most severe detriment
being the developmental defects collectively referred to as fetal alcohol syndrome (FAS). In brain, FAS is
hallmarked by defects in gross morphology (e.g., microcephaly, hydrocephaly, porencephaly,
hydroanencephaly) that have been attributed to insult during corticogenesis. Prenatal chronic ethanol
exposure compromises the GABAergic system in the immature brain and, thus, inhibitory regulation,
contributing to increased susceptibility to seizures and deficits in sensory information processing associated
with FAS.
In this proposal, we ask whether chronic ethanol consumption (1-6% EtOH) during pregnancy leads to
abnormal development of the GABAergic system in the offspring. The overriding hypothesis is that the
abnormal disposition of the postnatal and mature cortex seen in FAS manifests itself early on in
corticogenesis by affecting the migration of primordial GABAergic interneurons to their usual laminar
positions within the neocortex. In rodent, these GABAergic interneurons arise extracortically primarily from
the medial ganglionic eminence (MGE) and migrate tangentially into the developing neocortex. In Specific
Aim 1, we will quantitatively assess the patterns and kinetics of the tangential migration of MGE-derived
cells with the specific hypothesis that the disruption of tangential migration is dependent on the dose and
time of ethanol insult in utero. Specific Aim 2 will employ real-time videomicroscopy in heterotypic and
heterochronic telencephalic slice cocultures to test the specific hypothesis that both cell intrinsic and
extrinsic mechanisms contribute to alter the pattern of tangentil migration with in utero ethanol. Specific Aim
3 will incorporate electrophysiological, gene profiling, and immunohistochemical approaches to test the
hypothesis that in utero ethanol exposure interacts with the GABAergic system to exert its effect on
tangential migration of MGE-derived cells.
Overall, this project will for the first time define the effect of ethanol consumption during early stages of
pregnancy on the embryonic development of a specific and important population of cells in the neocortex,
notably the GABAergic cortical interneurons. In the long run, the proposed studies will lay the groundwork
for assessing how disruptions of the cortical neuronal circuitry underlie many of the behavioral abnormalities
seen in FAS.
怀孕期间摄入乙醇可能对后代有害,危害最严重
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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Verginia Carmella Cuzon Carlson其他文献
Verginia Carmella Cuzon Carlson的其他文献
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{{ truncateString('Verginia Carmella Cuzon Carlson', 18)}}的其他基金
Project 7/8: INIA Stress and Chronic Alcohol Interactions: Cross-species studies of metabolic allostasis and altered striatal circuitry
项目 7/8:INIA 压力和慢性酒精相互作用:代谢动态平衡和纹状体回路改变的跨物种研究
- 批准号:
10590709 - 财政年份:2022
- 资助金额:
$ 4.2万 - 项目类别:
Project 7/8: INIA Stress and Chronic Alcohol Interactions: Cross-species studies of metabolic allostasis and altered striatal circuitry
项目 7/8:INIA 压力和慢性酒精相互作用:代谢动态平衡和纹状体回路改变的跨物种研究
- 批准号:
10409985 - 财政年份:2022
- 资助金额:
$ 4.2万 - 项目类别:
Functional consequences of fetal-alcohol-induced brain growth abnormalities identified with in utero MRI
子宫内 MRI 发现胎儿酒精引起的大脑生长异常的功能后果
- 批准号:
10398204 - 财政年份:2021
- 资助金额:
$ 4.2万 - 项目类别:
Functional consequences of fetal-alcohol-induced brain growth abnormalities identified with in utero MRI
子宫内 MRI 发现胎儿酒精引起的大脑生长异常的功能后果
- 批准号:
10590615 - 财政年份:2021
- 资助金额:
$ 4.2万 - 项目类别:
Gestational ethanol effects on dorsal striatal function and associated behaviors
妊娠期乙醇对背侧纹状体功能和相关行为的影响
- 批准号:
8810270 - 财政年份:2014
- 资助金额:
$ 4.2万 - 项目类别:
Gestational ethanol effects on dorsal striatal function and associated behaviors
妊娠期乙醇对背侧纹状体功能和相关行为的影响
- 批准号:
9042902 - 财政年份:2014
- 资助金额:
$ 4.2万 - 项目类别:
Gestational ethanol effects on dorsal striatal function and associated behaviors
妊娠期乙醇对背侧纹状体功能和相关行为的影响
- 批准号:
8838018 - 财政年份:2014
- 资助金额:
$ 4.2万 - 项目类别:
In utero ethanol exposure & development of GABAergic cortical interneurons
子宫内乙醇暴露
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7222441 - 财政年份:2006
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$ 4.2万 - 项目类别:
7/8: INIA Stress and Chronic Alcohol Interactions: Stress and Ethanol Self Administration in Monkeys
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Translational examination of alcohol-associated epigenetic signatures: from primates to rodents
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10056068 - 财政年份:1996
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