Astrocytic-neuronal mechanisms in memory formation and cognitive impairments

记忆形成和认知障碍中的星形胶质细胞神经元机制

基本信息

批准号：
8836594
负责人：
CRISTINA M ALBERINI
金额：
$ 49.35万
依托单位：
NEW YORK UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2016-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8836594
关键词：
Adult Agreement Alzheimer&apos s Disease Animal Model Anxiety Disorders Astrocytes Avoidance Learning Biological Bipolar Disorder Brain CCAAT-Enhancer-Binding Proteins Cognition Disorders Cognitive Coupling Cyclic AMP-Responsive DNA-Binding Protein Dementia Development Disease Genetic Transcription Glucose Goals Health High Prevalence Hippocampus (Brain)Impaired cognition Knowledge Laboratories Lead Learning Learning Disabilities Link Long-Term Potentiation Maintenance Mediating Memory Memory Disorders Memory impairment Mental Depression Mental Health Metabolic Modeling Molecular Mood Disorders Nature Neurons Phase Play Positioning Attribute Process Psyche structure Rattus Recruitment Activity Regulation Research Role Schizophrenia Short-Term Memory Stress Technology Therapeutic Time Translations autism spectrum disorder cognitive function conditioned fear extracellular glycogen metabolism glycogenolysis improved in vivo insight juvenile animal long term memory mature animal memory consolidation memory retention nervous system disorder novel prevent research study synaptic function tool transcription factor

项目摘要

DESCRIPTION (provided by applicant): Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Identifying mechanisms of long-term memory formation and targets that help in preventing or treating memory impairments is an important goal in mental health. Thus far, the studies of mechanisms underlying cognitive functions including memory have mainly focused on elucidating the contribution of neurons and neuronal networks. However, findings of the last few decades indicate that astrocytes actively participate in the regulation of synaptic functions including long-term plasticity and memory. Very little is known about the nature and functions of these astrocytic mechanisms. Furthermore, very little is known also about possible involvement of astrocytic functions in memory and cognitive impairments. Using a contextual fear conditioning memory task in rats we have recently identified a critical role of astrocytes- dependent metabolic coupling with neurons in long-term memory formation in rats. These findings show, for the first time to our knowledge, that, in a mammalian brain, astrocytes play a necessary and active role in long-term memory formation. This proposal aims at further investigating the biological mechanisms of astrocytes and their interactions with neurons in long-term memory formation and in memory impairments that accompany stress-related cognitive impairments. Importantly, mechanisms underlying memory formation during early development and in adulthood will be investigated to determine similarities and differences. Results from these studies should advance our knowledge of the biological mechanisms underlying memory formation and should lead to novel hypotheses and tools for understanding cognitive functions and preventing or reversing cognitive impairments linked to stress-related cognitive disorders.

描述（由申请人提供）：维持和促进健康的认知功能，其中最重要的记忆是心理健康研究的主要目标之一。确定长期记忆形成的机制和有助于预防或治疗记忆障碍的目标是心理健康的重要目标。到目前为止，包括记忆在内的认知功能的机制的研究主要集中在阐明神经元和神经元网络的贡献上。但是，过去几十年的发现表明，星形胶质细胞积极参与了包括长期可塑性和记忆在内的突触功能的调节。这些星形细胞机制的性质和功能知之甚少。此外，关于星形细胞功能可能参与记忆和认知障碍的可能参与也很少知道。使用大鼠的上下文恐惧调节记忆任务，我们最近确定了星形胶质细胞依赖性代谢耦合与神经元在大鼠长期记忆形成中的关键作用。据我们所知，这些发现首次表明，在哺乳动物的大脑中，星形胶质细胞在长期记忆形成中起着必要而积极的作用。该建议旨在进一步研究星形胶质细胞的生物学机制及其与长期记忆形成中的神经元的相互作用，以及与压力相关的认知障碍伴随的记忆障碍。重要的是，将研究早期发展和成年期间记忆形成的机制，以确定相似性和差异。这些研究的结果应提高我们对记忆形成潜在的生物学机制的了解，并应导致新的假设和工具，以理解认知功能，并防止或逆转与压力相关的认知障碍有关的认知障碍。