Effects of acetaminophen on prenatal brain development: an organoid model
对乙酰氨基酚对产前大脑发育的影响:类器官模型
基本信息
- 批准号:10510873
- 负责人:
- 金额:$ 23.7万
- 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:2022-08-15 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:AcetaminophenAcuteAddressAgeAminophenolsAnalgesic and AntipyreticAnimal ModelApoptosisAsiaAttention deficit hyperactivity disorderBehaviorBehavioralBirthBrainCellsChildCohort StudiesDataDevelopmentDiagnosisDiseaseDoseDrug usageElectrophysiology (science)Embryonic DevelopmentEpidemiologyEuropeExposure toFetusFeverFlow CytometryFragile X SyndromeFrequenciesGenesGenetic TranscriptionHeadHealthHepatotoxicityHourHumanHyperactivityImmunohistochemistryInjectionsIntakeKnowledgeLanguage DevelopmentLeadLong-Term EffectsMeasuresModelingMolecularMothersMotorNeuraxisNeurodevelopmental DisorderNeuronsOdds RatioOrganoidsPainParentsPathway interactionsPharmaceutical PreparationsPhenotypePopulationPregnancyPregnant WomenPropertyProteinsRattusRegression AnalysisReportingRett SyndromeReview LiteratureRiskSafetySecond Pregnancy TrimesterSignal TransductionSliceStudy modelsSymptomsSynapsesTestingTherapeuticThird Pregnancy TrimesterVirus DiseasesZebrafishadverse outcomeautism spectrum disorderbasebody systemcognitive functioncohortcraniofacial structuredensityepidemiological modelepidemiology studyexecutive functionexperiencefetalhuman fetal brainhuman stem cellsindexinginsightmulti-electrode arraysnervous system developmentneurodevelopmentneurogenesisneurotoxicityoffspringpostnatal developmentprenatalprenatal exposureprogramsresponsesingle-cell RNA sequencingstem cell modelsynaptogenesistranscriptome
项目摘要
SUMMARY
Acetaminophen (N-acetyl-p-aminophenol (APAP), also known as paracetamol) is widely used in pregnancy for
pain and fever reduction. However, an increasing number of studies suggest that APAP could negatively
influence fetal and early postnatal development, including multiple organs systems. Regarding
neurodevelopment, epidemiological studies of large cohorts have reported a significantly increased risk of
attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children prenatally
exposed to APAP. In particular, fetal brain development during the second and third trimesters of pregnancy
appears especially vulnerable to APAP based on the epidemiological and animal model studies. Despite strong
evidence for potential adverse consequences to the fetus, the mechanism by which APAP impacts human fetal
brain remains unexplored. Here, we are proposing to use human functional brain organoid models to address
this question. Brain organoids are a perfect fit for this project because they recapitulate human fetal brain
development at the transcriptional and network activity levels, as demonstrated by us and others. We
hypothesize that APAP impacts fetal brain development by dysregulating transcriptional programs
involved in early neurogenesis and synaptic signaling. We will test this hypothesis through the following
Specific Aims: (1) Identify cellular and molecular pathways, cell populations, and co-expression modules
dysregulated by APAP exposure during fetal brain development; (2) Investigate synaptic and long-term
oscillatory network activity phenotypes in response to APAP exposure to evaluate its impact on brain function.
Our study will fill in the knowledge gap regarding the safety of APAP exposure in pregnancy using relevant
human-derived brain organoid models. In addition, it will provide molecular mechanisms by which APAP could
disrupt fetal brain development and lead to neurodevelopmental diseases.
总结
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)
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LILIA M IAKOUCHEVA其他文献
LILIA M IAKOUCHEVA的其他文献
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Effects of acetaminophen on prenatal brain development: an organoid model
对乙酰氨基酚对产前大脑发育的影响:类器官模型
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