Durable changes in cognition and astrocytic bioenergetics after drug experience

药物体验后认知和星形细胞生物能学的持久变化

基本信息

批准号：
9144361
负责人：
PAUL E. GOLD
金额：
$ 22.28万
依托单位：
SYRACUSE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-15 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9144361
关键词：
Area Astrocytes Attenuated Behavior Behavioral Bioenergetics Biology Brain Brain region Cocaine Cognition Cognitive Corpus striatum structure Down-Regulation Drug Exposure Energy Metabolism Energy-Generating Resources Equilibrium Exposure to Future Glucose Glycogen Goals Health Hippocampus (Brain)Impaired cognition Impairment Injection of therapeutic agent Investigation Laboratories Laboratory Finding Learning Long-Term Effects Maze Learning Measures Memory Morphine Morphology Nature Neuroglia Neuronal Plasticity Neurons Output Performance Pharmaceutical Preparations Pharmacotherapy Production Rattus Regulation Reporting Role Structure System Testing Time Training Up-Regulation Vascular blood supply area striata base brain behavior cocaine exposure cognitive change cognitive function cognitive process drug of abuse experience extracellular glycogenolysis neurochemistry novel strategies relating to nervous system research study response

项目摘要

DESCRIPTION (provided by applicant): Exposure to drugs of abuse alter neuronal functioning, evident as both altered biology of the neurons and altered behaviors. Some of these changes long outlast the drug exposure. In parallel, there is also considerable evidence that exposure to drugs of abuse alters glial astrocyte morphology and function. Astrocytic glycogen serves as an energy reserve in the brain and its degradation is initiated during neuronal activation. Glycogen is metabolized on demand to lactate, which is then transported into neurons to serve as an energy substrate. Recent findings indicate that the contribution of astrocytes to energy metabolism in neurons is a key regulator of memory and neural plasticity. However, changes in astrocyte form and function have not been directly associated with the alteration in cognitive functions after exposure to drugs of abuse. We recently found that learning experiences, obtained during a single 1-hr training session, alter astrocytic glycogen storage and lactate production 30 days later in rats; these changes vary with task and brain area. This project extends these findings to test the effects of cocaine and morphine treatments on changes in glycogen levels and lactate production up to 30 days after drug exposure together with functional measures of astrocyte activity during later learning. Based on previously identified cognitive changes that differ after morphine and cocaine exposure, a multiple memory systems approach is applied here using neurochemical measures in striatum and hippocampus together with training on tasks that differentially engage these brain areas. This project will tes the hypotheses that cocaine and morphine exposure result in long-term changes in the contributions of astrocytes to brain energy metabolism with important consequences for enduring effects of drug experience on cognitive functions. The findings from these experiments may be foundational for future investigations into the nature of long-lasting changes in cognition and brain after drug experience. The contributions of astrocytes to altered bioenergetics after drug exposure, together with altered learning and memory abilities, may open new approaches to understanding and ameliorating the long-term consequences of drug exposures on brain and behavior.

描述（由适用提供）：暴露于滥用药物会改变神经元功能，这是神经元的生物学改变和行为改变的证据。其中一些变化长期超过了药物的暴露。同时，也有大量证据表明，暴露于滥用药物会改变神经胶质的星形胶质细胞形态和功能。星形细胞糖原可作为大脑的能量储备，其降解是在神经元激活期间启动的。按需需要将糖原代谢，然后将其转运到神经元中作为能量底物。最近的发现表明，星形胶质细胞对神经元能量代谢的贡献是记忆和神经可塑性的关键调节剂。但是，星形胶质细胞形式和功能的变化与暴露于滥用药物后认知功能的改变并不直接相关。我们最近发现，在30天后在大鼠中，在一次1小时训练中获得的学习经验改变了星形胶质细胞的储存和乳酸的产生；这些变化因任务和大脑区域而异。该项目扩展了这些发现，以测试可卡因和吗啡处理对药物暴露后30天的糖原水平和乳酸产生变化的影响，并在以后学习过程中的星形胶质细胞活性测量。基于先前确定的认知变化，在吗啡和可卡因暴露后，使用纹状体和海马中的神经化学测量以及对这些大脑区域不同的任务进行培训，在此应用多个记忆系统方法。该项目将提出可卡因和吗啡暴露导致星形胶质细胞对脑能量代谢的贡献的长期变化的假设，对药物经验对认知功能的持久影响产生了重要的后果。这些实验中的发现可能是基本的基础，用于未来对药物经验后认知和大脑长期变化的性质进行投资。星形胶质细胞对药物暴露后改变生物能力的贡献，以及改变的学习和记忆能力，可以开放新的方法，以理解和改善药物暴露对脑和行为的长期后果。