Volatile organic compound effects on brain and behavior
挥发性有机化合物对大脑和行为的影响
基本信息
- 批准号:10118080
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2021-03-31
- 项目状态:已结题
- 来源:
- 关键词:3-nitrotyrosineAddressAffectAgingAnimal ModelAreaAutopsyBehaviorBehavior assessmentBehavioralBiologicalBrainChronicCorpus striatum structureDetectionDevelopmentDopamineDorsalDoseExhibitsExperimental DesignsExposure toFaceFamilyGoalsGulf WarHarvestHealthHealth Care CostsHigh Pressure Liquid ChromatographyIndividualIngestionKnowledgeLongitudinal StudiesMeasuresMedicalMedical centerMethodsMicrogliaModelingMolecular AnalysisMotorNerve DegenerationNeurodegenerative DisordersNeurologicNeuronsNitratesOhioOlive oil preparationOrangesParkinson DiseasePathologyPilot ProjectsPoisonPoisoningPollutionProteinsPublic HealthPublishingRattusRecording of previous eventsResearchResearch DesignResearch PersonnelRodentSignal TransductionSourceStainsStressSubstantia nigra structureTestingTetrachloroethyleneTimeTissuesToxic effectToxicologyTrichloroethyleneTyrosine 3-MonooxygenaseUniversitiesVeteransWaterWater SupplyWorkbasebehavior testbrain behaviorbrain tissuecontaminated drinking watercontaminated waterdisease registrydopaminergic neurondosagedrinking waterexposed human populationground waterhealth assessmentmotor impairmentneurobehavioralneuroinflammationneuropathologyneurotoxicneurotoxicitynigrostriatal pathwaypars compactaprogramsresponsevolatile organic compound
项目摘要
Abstract
Up to one million individuals stationed at Camp Lejeune, NC may have been poisoned by
exposure to volatile organic compounds (VOCs) that had leached into the base drinking water
from 1953 – 1987. The VA is now covering the health costs for Camp Lejeune veterans, civilian
staff, and the resident families stationed at the base during that time for a variety of health
conditions, including Parkinson's Disease (PD). Still, two of the main contaminants implicated in
the toxic effects, trichloroethylene (TCE) and tetrachloroethylene (PCE), have yet to be shown
to cause PD at the levels within 100-fold of those documented to have existed in the drinking
water. TCE can cause PD at very high levels when given sub-chronically to rodents, and PCE
has only been suggested to elicit PD in the animal models when it is combined with TCE.
Neither the duration nor the dose of TCE or PCE used in past studies approximated the Camp
Lejeune average exposure estimates. Therefore, the goal of this pilot project is to document
the basic parameters necessary for chronic TCE (with and without PCE) exposure to cause
behavioral and biological signs of PD neurotoxicity when delivered chronically in the water
supply. Our working hypothesis is that chronic TCE+PCE ingestion through drinking water
leads to behavioral changes indicative of underlying neuroinflammation in the substantia nigra
pars compacta (SNPC) of the brain that, with continued ingestion, eventually leads to
neurodegeneration of the SNPC dopamine (DA) neurons (i.e. development of PD). The testing
of this hypothesis will occur by assessing function and neuropathology in exposed rats through
2 aims. Aim 1 will focus upon determining the possible contribution of drinking water TCE to PD
pathology. An established toxic sub-chronic daily gavage TCE dose will be extended over a 6
month period in the drinking water to determine if the total cumulative exposure predicts the
induction of PD or if daily high concentrations are necessary for TCE to induce PD. Following a
similar experimental design, Aim 2 will determine if the addition of PCE to TCE-contaminated
drinking water potentiates the induction of PD. Functional assessments, via behavioral testing,
will occur during and following TCE or TCE+PCE exposure. At each time-point, rats will be
assessed for motor coordination and sensorimotor reactivity. Upon completion of the last post-
exposure behavioral test, all rats will have their brains harvested for subsequent brain
assessments. The brains will be assessed for DA and DA-metabolite levels in the striatum and
neuroinflammation/neuropathology in the SNPC. These post-mortem analyses, combined with
the repeated behavioral testing over time, will provide the first evidence if chronic drinking water
contamination by TCE or TCE+PCE are sufficient to cause a PD-like motor impairments or
outright PD.
抽象的
驻扎在北卡罗来纳州莱吉恩营地的一百万个人可能被毒死
接触挥发性有机化合物(VOC),这些化合物已进入基础饮用水
从1953年至1987年。VA现在涵盖了Lejeune Camp退伍军人,平民的健康费用
员工和居民家庭在那段时间内驻扎在基地
疾病,包括帕金森氏病(PD)。尽管如此,在
毒性作用,三氯乙烯(TCE)和四氯乙烯(PCE)尚未显示
在饮酒中引起的PD以内的PD在100倍之内
水。当下给啮齿动物时,TCE可能会在很高的水平上引起PD,并且PCE
仅建议将动物模型与TCE结合时引起PD。
过去研究中使用的持续时间和TCE或PCE的剂量均未近似camp
Lejeune平均暴露估计。因此,该试点项目的目标是记录
慢性TCE(有或没有PCE)暴露所必需的基本参数会导致
长期在水中递送PD神经毒性的行为和生物学体征
供应。我们的工作假设是慢性TCE+PCE从饮用水中摄入
导致行为变化,指示尼格拉统治中潜在的神经炎症
大脑的pars comcacta(SNPC),随着持续摄入,最终导致
SNPC多巴胺(DA)神经元的神经变性(即PD的发展)。测试
通过通过评估暴露大鼠的功能和神经病理学来实现这一假设
2目标。 AIM 1将集中于确定饮用水对PD的可能贡献
病理。已建立的有毒亚基剂每日粘液剂量将在6上延长
饮用水中的月期,以确定总累积暴露预测是否
如果TCE诱导PD或每日高浓度诱导PD。遵循
类似的实验设计,AIM 2将确定在TCE污染中添加PCE是否添加
饮用水潜力PD的诱导。功能评估,通过行为测试,
将在TCE或TCE+PCE暴露期间发生。在每个时间点,老鼠将是
评估了运动配位和感觉运动反应性。最后一职完成后
暴露行为测试,所有大鼠的大脑都将用于随后的大脑
评估。将对纹状体中的DA和DA-代谢物水平进行评估,并
SNPC中的神经炎症/神经病理学。这些验尸分析,结合
随着时间的推移,反复进行的行为测试将提供第一个证据,如果慢性饮用水
TCE或TCE+PCE污染足以引起PD样运动障碍或
彻底的PD。
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)
专利数量(0)
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Kevin D. Beck其他文献
Choice and motor impulsivity in Veterans with mild traumatic brain injury with and without history of suicide attempt
- DOI:
10.1016/j.psychres.2024.116265 - 发表时间:
2024-12-01 - 期刊:
- 影响因子:
- 作者:
Alejandro Interian;Catherine E. Myers;Lisa A. Brenner;Regan Sweeney;Terra Osterberg;Vibha Reddy;Meghan Barnhart;Lauren St. Hill;Rachael B. Miller;Kevin D. Beck;Tara P. Cominski;Chi C. Chan;Keith M. Shafritz;Marianne S. Goodman;Erin A. Hazlett - 通讯作者:
Erin A. Hazlett
Kevin D. Beck的其他文献
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{{ truncateString('Kevin D. Beck', 18)}}的其他基金
CTBI: Traumatic brain injury-induced inflammation effects on cognitive evaluations and response inhibition: Mechanisms of increased risk for suicidality
CTBI:创伤性脑损伤诱发的炎症对认知评估和反应抑制的影响:自杀风险增加的机制
- 批准号:
10515654 - 财政年份:2019
- 资助金额:
-- - 项目类别:
CTBI: Traumatic brain injury-induced inflammation effects on cognitive evaluations and response inhibition: Mechanisms of increased risk for suicidality
CTBI:创伤性脑损伤诱发的炎症对认知评估和反应抑制的影响:自杀风险增加的机制
- 批准号:
10292963 - 财政年份:2019
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An integrated startle response, fear conditioning, and muscle tremor analysis system for rodents
啮齿类动物的综合惊吓反应、恐惧调节和肌肉震颤分析系统
- 批准号:
9794634 - 财政年份:2019
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A comprehensive physiology and behavior system for homecage-based assessments
用于基于家庭笼的评估的综合生理学和行为系统
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9910014 - 财政年份:2019
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Neuroinflammation and abnormal behavior following combined chemical exposures and bacterial infection
化学品暴露和细菌感染联合后的神经炎症和异常行为
- 批准号:
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Role for Glucose-Inhibited Orexin Neurons in Weight Regain Following Dieting
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Annual meeting of the Organization for the Study of Sex Differences
性别差异研究组织年会
- 批准号:
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Neural mechanisms of extinction-resistant avoidance behavior
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- 批准号:
7931236 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Neural mechanisms of extinction-resistant avoidance behavior
抗灭绝回避行为的神经机制
- 批准号:
8394591 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Neural mechanisms of extinction-resistant avoidance behavior
抗灭绝回避行为的神经机制
- 批准号:
8195590 - 财政年份:2010
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