Endocrine Disrupting Chemicals, Epigenetic Alterations, and Autism-Like Behaviors in the Highly Social California Mouse Model
高度社会化加州小鼠模型中的内分泌干扰化学物质、表观遗传改变和自闭症样行为
基本信息
- 批准号:10016304
- 负责人:
- 金额:$ 37.82万
- 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:2016-09-01 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AdultAffectAffectiveAmygdaloid structureAnimal ModelAnimalsAnxietyBehaviorBehavior DisordersBehavioralBehavioral SymptomsBrainBrain regionCaliforniaCandidate Disease GeneCategoriesChemicalsChildClinicalCognitiveCognitive deficitsDNA MethylationDataDeer MouseDevelopmentDiagnosisDiseaseDoseEndocrine DisruptorsEnvironmental Risk FactorEpigenetic ProcessEquipmentEstrogensEthinyl EstradiolEtiologyExhibitsExposure toFemaleGene ExpressionGenesGeneticGenisteinGoalsHandHippocampus (Brain)HumanHypothalamic structureImpairmentIncidenceIndividualInfant formulaInternationalLinkMeasuresMicroRNAsMothersMusParentsPathway AnalysisPathway interactionsPatientsPatternPerinatal ExposurePeromyscusPhytoestrogensPlantsProcessReportingResearchRiskRodentSame-sexSex BehaviorSiblingsSocietiesStatistical Data InterpretationStudy modelsTestingTransgenic MiceTranslatinganxiety-like behaviorautism spectrum disorderautistic childrenbasebehavioral phenotypingbisphenol Acandidate markerdisorder riskenvironmental chemicalexperiencein uteromalemethylation patternmother nutritionmouse modelneurobehavioralneurobehavioral disordernoveloffspringprenatal exposurerelating to nervous systemremediationrepetitive behaviorsexsocialsocial organizationsoysteroid hormonetraittranscriptometranscriptomicstreatment groupway finding
项目摘要
Project Summary
Increasing numbers of children are being diagnosed with autism spectrum disorders (ASD and related
neurobehavioral disorders. Based on the rising incidence that is not explained by genetics alone, it has been
postulated that in utero exposure to environmental chemicals may increase the risk for these disorders.
Perinatal exposure of children through the mother to endocrine disrupting chemicals (EDCs), including
bisphenol A (BPA), has been linked to ASD. To establish potential causation and underlying mechanisms,
it is important to test these chemicals in a relevant animal model species, where the clinical core
behavioral symptoms exhibited by ASD children can be replicated.
Most ASD animal model studies to date have employed transgenic mice. However, these animals often fail to
replicate all of the core ASD-like behaviors. The monogamous, biparental, and highly communicative California
mouse (Peromyscus californicus) provides a complementary animal model for ASD research. We have
previously demonstrated that neurobehavioral programming in California mice is especially vulnerable to BPA.
Developmentally exposed males demonstrate compromised socio-sexual behaviors, and their female siblings
exhibit heightened anxiety, reminiscent of children with ASD. Both males and females developmentally
exposed to BPA go on to become poor parents as adults.
We will test the hypothesis that early exposure to BPA and genistein (G), a phytoestrogen present in
soy products- including baby formulas, results in ASD-like behavioral disorders in California mice. The
first goal will be to ascertain whether early exposure to BPA, G, and the combination of the two EDCs results in
behavioral deficits observed in ASD patients. The second goal will be to determine whether males and females
exposed to these chemicals show gene expression/DNA methylation/miRNA (miR) changes in the brain sub-
regions (amygdala, hypothalamus and hippocampus) governing these traits that may underlie the disrupted
behavioral phenotypes.
Specific Aims are to: 1) Test whether developmental exposure of male and female F1 California mice to BPA,
G, and BPA + G affects behavioral domains disrupted in ASD children, such as social-sexual-communicative,
cognitive, anxiety/neuro-affective, and repetitive behaviors. 2) Test whether these individual and combined
EDCs affect global transcriptomic profiles in the amygdala, hippocampus and hypothalamus in F1 males and
females that may underpin the EDC-induced behavioral disruptions. 3) Determine whether these treatments
induce DNA methylation and miR changes in the amygdala, hippocampus and hypothalamus in both F1 sexes
and perform a comprehensive correlation analysis to link the various bio-molecular and behavioral
disturbances. Data will likely provide novel candidate biomarkers that can be used to diagnose and in potential
preventative/remediation strategies in children at-risk for ASD due to early exposure to these EDCs.
项目总结
项目成果
期刊论文数量(23)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Brain Sexual Differentiation and Requirement of SRY: Why or Why Not?
- DOI:10.3389/fnins.2017.00632
- 发表时间:2017
- 期刊:
- 影响因子:4.3
- 作者:Rosenfeld CS
- 通讯作者:Rosenfeld CS
Long-Term Effects of Developmental Exposure to Oxycodone on Gut Microbiota and Relationship to Adult Behaviors and Metabolism.
- DOI:10.1128/msystems.00336-22
- 发表时间:2022-08-30
- 期刊:
- 影响因子:6.4
- 作者:
- 通讯作者:
Placental Changes in the serotonin transporter (Slc6a4) knockout mouse suggest a role for serotonin in controlling nutrient acquisition.
- DOI:10.1016/j.placenta.2021.09.021
- 发表时间:2021-11
- 期刊:
- 影响因子:3.8
- 作者:Mao J;Kinkade JA;Bivens NJ;Roberts RM;Rosenfeld CS
- 通讯作者:Rosenfeld CS
Disruption of global hypothalamic microRNA (miR) profiles and associated behavioral changes in California mice (Peromyscus californicus) developmentally exposed to endocrine disrupting chemicals.
- DOI:10.1016/j.yhbeh.2020.104890
- 发表时间:2021-03
- 期刊:
- 影响因子:3.5
- 作者:Kaur S;Kinkade JA;Green MT;Martin RE;Willemse TE;Bivens NJ;Schenk AK;Helferich WG;Trainor BC;Fass J;Settles M;Mao J;Rosenfeld CS
- 通讯作者:Rosenfeld CS
Sexually Dimorphic Effects of Aromatase on Neurobehavioral Responses.
- DOI:10.3389/fnmol.2018.00374
- 发表时间:2018
- 期刊:
- 影响因子:4.8
- 作者:Shay DA;Vieira-Potter VJ;Rosenfeld CS
- 通讯作者:Rosenfeld CS
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{{ truncateString('R. MICHAEL ROBERTS', 18)}}的其他基金
Induced Pluripotent Stem Cells from Swine: application to genetic modification
猪诱导多能干细胞:在基因改造中的应用
- 批准号:
8618911 - 财政年份:2012
- 资助金额:
$ 37.82万 - 项目类别:
Induced Pluripotent Stem Cells from Swine: application to genetic modification
猪诱导多能干细胞:在基因改造中的应用
- 批准号:
8436202 - 财政年份:2012
- 资助金额:
$ 37.82万 - 项目类别:
Induced Pluripotent Stem Cells from Swine: application to genetic modification
猪诱导多能干细胞:在基因改造中的应用
- 批准号:
8813486 - 财政年份:2012
- 资助金额:
$ 37.82万 - 项目类别:
Induced Pluripotent Stem Cells from Swine: application to genetic modification
猪诱导多能干细胞:在基因改造中的应用
- 批准号:
8183121 - 财政年份:2012
- 资助金额:
$ 37.82万 - 项目类别:
Pluripotent human stem cells as models for normal and diseased trophoblast
多能人类干细胞作为正常和患病滋养层的模型
- 批准号:
8028598 - 财政年份:2010
- 资助金额:
$ 37.82万 - 项目类别:
Pluripotent human stem cells as models for normal and diseased trophoblast
多能人类干细胞作为正常和患病滋养层的模型
- 批准号:
8392183 - 财政年份:2010
- 资助金额:
$ 37.82万 - 项目类别:
Pluripotent human stem cells as models for normal and diseased trophoblast
多能人类干细胞作为正常和患病滋养层的模型
- 批准号:
8770034 - 财政年份:2010
- 资助金额:
$ 37.82万 - 项目类别:
Pluripotent human stem cells as models for normal and diseased trophoblast
多能人类干细胞作为正常和患病滋养层的模型
- 批准号:
8206784 - 财政年份:2010
- 资助金额:
$ 37.82万 - 项目类别:
INTERACTION BETWEEN BLASTOCYST AND UTERINE EPITHELIUM
囊胚和子宫上皮之间的相互作用
- 批准号:
7601305 - 财政年份:2007
- 资助金额:
$ 37.82万 - 项目类别:
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社交媒体上的情感病毒传播:文化和理想情感的作用
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Affective Rendering ? Toward the Realization of Affect Adapted Image Synthesis
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A Study by Means of Analysis of Structure of Covariunce, on Factors which Affect Japanese Language Acquisition and Mother Tongue Maintenance of Children from Overseas-an Integral Study of Cognitive Linguistic / Affective / Socio Cultural Factors-
协方差结构分析影响海外儿童日语习得和母语维持的因素研究-认知语言/情感/社会文化因素的综合研究-
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