Mitigating Developmental Neurotoxicity Through Maternal and Offspring Exercise
Mitigating Developmental Neurotoxicity Through Maternal and Offspring Exercise
批准号:
10725969
负责人:
Christine Perdan Curran
金额:
$14.0万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-07 至 2025-08-31
关键词:
Adverse effectsAerobic ExerciseAffinityAromatic Polycyclic HydrocarbonsAryl Hydrocarbon ReceptorBehaviorBehavioralBenzo(a)pyreneBiochemicalBrainBrain-Derived Neurotrophic FactorCYP1A2 geneCarcinogensChemicalsChildCognitiveDataDevelopmentDopamineEnsureExerciseExhibitsExposure toFoodGene ExpressionGeneral PopulationGeneticGenetic Predisposition to DiseaseGenetic studyGoalsGovernmentHealthHippocampusHormonesHumanImpairmentInterventionKnock-outLeadLearningLifeLiteratureMemoryMemory impairmentMethodsModificationMolecularMoodsMothersMotorMusNeurologicNeurologic DeficitNeurological outcomeNeurotransmittersNeurotrophic Tyrosine Kinase Receptor Type 2NorepinephrinePerformancePilot ProjectsPlasmaPopulationPredispositionPregnancyRegimenReportingRiskRunningSerotoninSignal TransductionStressTestingWildfireanxiety reductionanxiety-like behaviorbrain healthcigarette smokedevelopmental neurotoxicityearly life exposureexercise intensityexercise regimenexposed human populationhealth of the motherimprovedknock-downmorris water mazemotor deficitmouse modeloffspringpollutantprenatalprenatal stresspupreceptorrelative effectivenesstraffic-related air pollution
中文摘要
项目总结/文摘
英文摘要
Project Summary/Abstract
Benzo[a]pyrene (BaP) is a known carcinogen and ranked 8th on the U.S. government’s Priority
Pollutants List while the entire class of compounds (polycyclic aromatic hydrocarbons or PAHs) ranks 9th.
Human exposures are widespread from traffic-related air pollution, wildfires, cigarette smoke, and grilled foods
and nearly impossible to avoid. Recent human studies found strong correlations between prenatal PAH
exposure and persistent cognitive and behavioral deficits in exposed children. We recently reported results
from a mouse study demonstrating that genetic differences in the aryl hydrocarbon receptor (AHR) and
CYP1A2 increase risk following developmental exposure to BaP. AhrbCyp1a2(-/-) mice with the high-affinity
AHR and AhrdCyp1a2(-/-) mice with the poor-affinity receptor both had impaired performance in the Morris
water maze test of spatial learning and memory. High-affinity Ahr knockouts also had motor deficits in Rotarod,
and poor-affinity knockouts exhibited higher levels of anxiety-like behavior. The benefits of regular exercise on
brain health are well established, but considerably less is known about the effects of exercise during
pregnancy on the health of the mother and brain function in her offspring. The neurological benefits of exercise
include increased levels of brain-derived neurotrophic factor (BDNF) and beneficial modifications of
neurosignaling by serotonin, dopamine and noradrenaline. The mechanism of action for aerobic exercise
benefits on hippocampal dependent learning and memory were directly tied to BDNF signaling. Both maternal
and offspring exercise have been successful in reversing spatial learning and memory deficits induced by
prenatal stress. Exercise during early life has additional benefits on improving mood and reducing levels of
stress hormones whereas anxiety-like behavior is increased in mice with a knockdown of the BDNF receptor
TrkB. We conducted pilot studies in C57BL/6J mice and found that both maternal and offspring voluntary wheel
running increased circulating BDNF levels. Our proposed studies will use aerobic exercise to increase
BDNF levels in offspring exposed to BaP during early brain development with the goal of rescuing the
neurological deficits observed in our previous studies. First, we will compare the relative effectiveness of
four different exercise treatments and ensure they do not cause harm to the dam or pups. Next, we will use the
exercise regimen determined to be safe and most effective in an attempt to rescue learning and memory and
motor deficits and to reduce anxiety-like behavior in our most susceptible mouse lines.The translational value
of these studies is high, because we seek to identify the minimum level of exercise necessary to produce
beneficial effects. This greatly increases the feasibility of compliance in the human population.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Society for Birth Defects Research and Prevention 2020-2024 Annual Meetings
-
批准号:10171834
-
项目类别:
-
资助金额:$0.35万
-
财政年份:2020
-
负责人:Christine Perdan Curran
-
依托单位:
Society for Birth Defects Research and Prevention 2020-2024 Annual Meetings
-
批准号:10412951
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2020
-
负责人:Christine Perdan Curran
-
依托单位:
Society for Birth Defects Research and Prevention 2020-2024 Annual Meetings
-
批准号:10038659
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2020
-
负责人:Christine Perdan Curran
-
依托单位:
Genetic Susceptibility to Developmental Benzo[a]pyrene Neurotoxicity
-
批准号:10730699
-
项目类别:
-
资助金额:$42.0万
-
财政年份:2019
-
负责人:Christine Perdan Curran
-
依托单位:
Genetic Susceptibility to PCB-induced Motor Dysfunction
-
批准号:8290842
-
项目类别:
-
资助金额:$40.18万
-
财政年份:2012
-
负责人:Christine Perdan Curran
-
依托单位:
Genetic Susceptibility to PCB-induced Motor Dysfunction
-
批准号:8894242
-
项目类别:
-
资助金额:$1.72万
-
财政年份:2012
-
负责人:Christine Perdan Curran
-
依托单位:
GENETIC SUSCEPTIBILITY TO PCB-INDUCED DEVELOPMENTAL NEUROTOXICITY
-
批准号:8360118
-
项目类别:
-
资助金额:$3.32万
-
财政年份:2011
-
负责人:Christine Perdan Curran
-
依托单位:
GENETIC SUSCEPTIBILITY TO PCB-INDUCED DEVELOPMENTAL NEUROTOXICITY
-
批准号:8168298
-
项目类别:
-
资助金额:$3.36万
-
财政年份:2010
-
负责人:Christine Perdan Curran
-
依托单位:
海外基金