Mechanisms Underlying Learning Deficits Caused by Paternal Cocaine Taking

父亲吸食可卡因导致学习障碍的机制

基本信息

批准号：
9915862
负责人：
Mathieu Wimmer
金额：
$ 18.02万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
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：
2016-05-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9915862
关键词：
Adult Adult Children Agonist Analgesics Animal Model Animals Anxiety Behavior Behavioral Biochemical Biological Assay Biological Markers Brain Child Chronic Cocaine Cocaine Abuse Cocaine Dependence Cognitive deficits Collaborations DNA DNA Sequence Data Development Drug usage Drug user Electrophysiology (science)Environmental Risk Factor Epigenetic Process Fathers Frequencies Future Generations Gene Expression Generations Genetic Transcription Glutamate Receptor Glutamates Health High Pressure Liquid Chromatography Hippocampus (Brain)Histones Illicit Drugs Impaired cognition Impairment Infusion procedures Inherited Learning Ligands Location Marijuana Measures Mediating Memory Memory impairment Modeling Molecular N-Methyl-D-Aspartate Receptors N-terminal Neurocognition Neurocognitive Deficit Outcome Parents Pharmaceutical Preparations Phenotype Physiology Post-Translational Protein Processing Property Proteins Proteomics Rattus Receptor Signaling Research Proposals Self Administration Serine Slice Specificity Substance abuse problem Synapses Synaptic plasticity Tail Techniques Testing Time Training Translating United States Voltage-Clamp Technics Western Blotting addiction base behavior influence cocaine exposure cocaine use cognitive function drug of abuse experience experimental study glutamatergic signaling hippocampal pyramidal neuron histone modification interest long term memory male neural circuit new therapeutic target object recognition offspring patch clamp psychostimulant public health relevance receptor receptor expression relating to nervous system spatial memory synaptic function therapeutic development trafficking

项目摘要

DESCRIPTION (provided by applicant): A growing body of evidence indicates that environmental information can be transmitted from parents to progeny. Thus, epigenetic changes in the mammalian germline can act as transgenerational carriers of environmental perturbations. Cocaine addiction remains a significant health problem in the United States and chronic cocaine use is associated with neurocognitive deficits. However, it remains unclear whether cocaine abuse in parents translates to reduced cognitive function in their offspring. This proposal will focus on the effects of paternal cocaine taking on memory formation in offspring using a rat model of cocaine addiction. We found that offspring and grand-offspring of cocaine-exposed fathers (sires) have spatial learning deficits and impaired hippocampal synaptic plasticity. In Specific Aim 1, we hypothesize that increasing NMDA receptor signaling will ameliorate learning and synaptic plasticity deficits caused by paternal cocaine taking. In Specific Aim 2, we will evaluate basal synaptic function, NMDA receptor signaling and epigenetic processes in the hippocampus of the descendants of cocaine-exposed sires. Taken together, this proposal will attempt to illuminate the mechanisms underlying learning deficits that are caused by paternal cocaine taking.

描述（由适用提供）：越来越多的证据表明可以将环境信息从父母传播到后代。这就是哺乳动物种系的表观遗传变化可以充当环境扰动的转化载体。在美国，可卡因成瘾仍然是一个重大健康问题，慢性可卡因使用与神经认知缺陷有关。但是，尚不清楚父母中的可卡因滥用是否转化为后代的认知功能降低。该建议将重点介绍父亲可卡因使用可卡因成瘾的大鼠模型在后代中对记忆形成的影响。我们发现，可卡因暴露的父亲（父亲）的后代和盛大的春季具有空间学习缺陷和海马合成可塑性受损。在特定的目标1中，我们假设增加NMDA受体信号传导将改善由父亲可卡因引起的学习和合成可塑性缺陷。具体 AIM 2，我们将评估可卡因暴露于可卡因的后代海马中的基本突触功能，NMDA受体信号传导和表观遗传过程。综上所述，该提案将试图阐明学习的基本机制定义由可卡因服用引起的。