Transgenerational effect of gestational ethanol exposure
妊娠期乙醇暴露的跨代效应
基本信息
- 批准号:8969729
- 负责人:
- 金额:$ 18.7万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-02-05 至 2018-01-31
- 项目状态:已结题
- 来源:
- 关键词:AdolescenceAdolescentAffectAlcohol abuseAlcohol consumptionAlcoholismAlcoholsAminobutyric AcidsAnimal ModelAnteriorAreaBase PairingBehavior TherapyBrainBrain regionBreedingCenters for Disease Control and Prevention (U.S.)Cognitive deficitsDNA MethylationDataDevelopmental Delay DisordersDiseaseEnvironmental Risk FactorEpigenetic ProcessEthanolExposure toFemaleFetal Alcohol ExposureFigs - dietaryFutureGene TargetingGenerationsGenesGenetic MarkersGerm LinesGrowthHumanInfantInvestigationLaboratoriesLifeMammalsMedialMediatingNucleus AccumbensOpioid ReceptorPerinatal ExposurePharmaceutical PreparationsPhenotypePrefrontal CortexPregnancyPregnant WomenProbabilityPropertyProteinsPsychological reinforcementPubertyPublic HealthRattusReflex actionResearchResolutionRiskRodentSyndromeSystemTechniquesTestingTransferenceUterusVariantVentral Tegmental AreaWaterWorkalcohol effectalcohol exposurealcohol rewardalcohol sensitivityalcohol use disorderanimal breedingbinge drinkingcingulate cortexfetalgamma-Aminobutyric Acidgenome-widehypnoticinnovationinterestmalemodel developmentneuromechanismoffspringplant fungipostnatalprenatalprenatal exposureprogramspublic health relevancereceptor expressionresearch studystatisticstraittransgenerational epigenetic inheritancetransmission processwhole genome
项目摘要
DESCRIPTION (provided by applicant): Prenatal alcohol exposure has been shown to increase the probability of use and abuse of ethanol later in life. One question remaining to be answered is, can it also be transmitted across generations? Our data suggest that low/moderate ethanol exposure results in increased ethanol intake and reduced sensitivity to ethanol's hypnotic effects during puberty not only in those infant rats exposed to ethanol in the womb but also in their offspring. Our central hypothesis is that inheritance of ethanol use/abuse liability s transgenerational and associated with variations in DNA methylation in specific brain regions known to be involved in alcohols rewarding proper- ties. The transformative objective of the present proposal is to identify the specific genes in these brain areas that are involved in ethanol programming as well as the lineage involved in transgenerational transmission of the ethanol-exposed phenotype. This project uses an animal model of prenatal ethanol exposure to investigate the transmission of increased liability for ethanol abuse in the offspring directly exposed to alcohol in the womb and their progeny. Specific Aim 1 will determine the contribution of maternal and paternal lineages in the effect of gestational ethanol exposure on ethanol sensitivity and consumption in three generation of off- spring. This will be achieved through testing prenatally exposed animals and breeding male and female rats prenatally exposed (F1) to 1) ethanol, 2) water, or 3) non-manipulated in all possible combinations (9; see table in approach) to determine the lineage involved in transmission. Our hypothesis, that inheritance is through paternal lineage, will be tested by examining ethanol intake at postnatal day (PD) 14 and in adolescence, and sensitivity to the hypnotic effects (loss of righting reflex test) of ethanl at PD 42. Specific Aim 2 will identify the effect of ethanol exposure during gestation on genome-wide DNA methylation of F1 and F2 of the extreme lineage (affected lineage and control), using a whole-genome bisulfate sequencing technique. Results obtained after completion of this work will allow us to direct future work towards target genes involved in the transmission of ethanol-exposed phenotype, and to better understand the mechanisms involved in transgenerational inheritance of increased risk for ethanol abuse.
项目成果
期刊论文数量(0)
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Nicole Marguerite Cameron其他文献
Nicole Marguerite Cameron的其他文献
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{{ truncateString('Nicole Marguerite Cameron', 18)}}的其他基金
Transgenerational effect of gestational ethanol exposure
妊娠期乙醇暴露的跨代效应
- 批准号:
9215617 - 财政年份:2016
- 资助金额:
$ 18.7万 - 项目类别:
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