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Mechanisms of Pesticide-Induced Neurobehavioral Deficits: Relevance to ADHD

农药引起的神经行为缺陷的机制：与多动症的相关性

基本信息

批准号：
7487552
负责人：
Jason R Richardson
金额：
$ 54.43万
依托单位：
UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7487552
关键词：
Adverse effects Affect Amphetamines Animal Model Attention Attention deficit hyperactivity disorder Behavior Behavioral Behavioral Paradigm Child Clinical Complement Complex Data Development Disease Dopaminergic Cell Dose Embryo Environmental Risk Factor Etiology Exhibits Female Functional disorder Gender Genes Genetic Genetic Polymorphism Hyperactive behavior Impulsivity Incidence Laboratories Lead Link Mediating Methylphenidate Modeling Molecular Molecular Target Mus Neurons Nuclear Outcome Patients Pesticides Pregnant Women RNA Interference Research Personnel Risk Factors Role School-Age Population Severities Sex Characteristics Signal Transduction Symptoms Techniques Testing Therapeutic Agents Therapeutic Intervention United States Environmental Protection Agency Viral decamethrin dopamine system dopamine transporter gender preference gene environment interaction improved in utero in vivo insight male neurobehavioral neurochemistry novel pesticide exposure programs psychostimulant pyrethroid response transcription factor

项目摘要

DESCRIPTION (provided by applicant): Attention-deficit hyperactivity disorder (ADHD) is a clinically heterogeneous disorder characterized by core features of impulsivity, hyperactivity, and attention deficits. ADHD is estimated to affect 8-12% of school-aged children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors or gene-environment interactions may contribute to the etiology or clinical manifestation of ADHD. Dopamine transporter (DAT) polymorphisms and elevated expression of the DAT have been observed in ADHD patients, suggesting alterations in DAT levels may contribute to ADHD. Since environmental factors, such as pesticides, have been shown to alter DAT expression, we have hypothesized that in utero pesticide exposure may contribute to the incidence or severity of ADHD. Recent data from this laboratory have demonstrated that the offspring of mice exposed to low levels of the pyrethroid pesticide deltamethrin during development exhibit similar symptoms as observed in children with ADHD, including elevated DAT levels, hyperactivity, a paradoxical calming response to psychostimulants, behavioral deficits, and a male gender-preference of these effects. Importantly, the doses that elicited these effects were at or below the no observable adverse effect level (NOAEL) established by the EPA for deltamethrin. This is particularly notable because the NOAEL used by the EPA when making regulatory decisions on pesticides. Because there has been documented exposure of pregnant women to pyrethroids and pyrethroid use has increased dramatically in the last decade, it may be prudent to evaluate pesticide exposure as a potential risk factor for ADHD. Furthermore, these mice represent a novel animal model to test therapies for ADHD and provide insight into the basic mechanisms underlying this disorder. Here, the investigators propose three Specific Aims to investigate mechanisms underlying the effects of deltamethrin on the dopamine system and characterize the behavioral effects of developmental deltamethrin expsoure. The investigators will then use this information to exploit this novel model to identify molecular targets for therapeutic intervention in ADHD.

描述（由申请人提供）：