ERK5 in Learning and Memory

ERK5 在学习和记忆中的应用

基本信息

批准号：
8880278
负责人：
ZHENGUI XIA
金额：
$ 38.63万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8880278
关键词：
Abbreviations Address Adult Affect Area Brain Brain region Candidate Disease Gene Cognition Disorders Complement Data Discrimination Exercise Exhibits Extinction (Psychology)Fright Generations Genes Hippocampus (Brain)Knock-out Knockout Mice Lead Learning Lethal Genes Literature Location MAPK7 gene Maintenance Measures Mediating Memory Mental Depression Mental Health Mental disorders Mitogen-Activated Protein Kinases Mitotic Molecular Mouse Strains Mus Neuronal Differentiation Neuronal Plasticity Neurons Parahippocampal Gyrus Pattern Pharmaceutical Preparations Physiological Play Research Role Shock Signal Transduction Signaling Molecule Signaling Protein Staging Stem cells Synapses Technology Testing Time Training Transgenic Mice Transgenic Organisms adult neurogenesis base conditioned fear dentate gyrus foot improved in vivo insight interest irradiation killings morris water maze neurogenesis relating to nervous system selective expression spatial memory stem therapy development tool

项目摘要

DESCRIPTION (provided by applicant): Deficits in learning and memory are prominent features of many mental disorders. Understanding molecular mechanisms responsible for learning and memory are key to the development of therapies to improve learning and memory in the treatment of mental illness. Recent studies lead to the exciting idea that newly generated neurons in the adult dentate gyrus (DG) of the hippocampus may play a role in neural plasticity including hippocampal-dependent memory formation. Adult neurogenesis occurs in the DG of the mammalian brains including adult human brain under physiological conditions and newly generated neurons functionally integrate to the DG. Many factors, including depression and other mental illness may adversely affect hippocampal adult neurogenesis. In contrast, treatment with anti-depressants and exercise, an effective means to treat depression, enhance adult neurogenesis in the DG. Consequently, elucidation of basic molecular mechanisms regulating adult hippocampal neurogenesis and generation of definitive evidence supporting a role for adult neurogenesis in hippocampal-dependent memory formation is a critical and timely issue for mental health research. Although many studies have assessed the role of adult neurogenesis in hippocampal-dependent learning and memory, the results have been inconsistent, making it still highly controversial whether adult neurogenesis contributes to hippocampus-dependent memory formation. This proposal will test the hypothesis that ERK5 signaling-mediated adult neurogenesis plays a critical role in some but not all forms of hippocampal- dependent learning and memory.

描述（由申请人提供）：学习和记忆缺陷是许多精神障碍的显着特征。了解负责学习和记忆的分子机制是开发改善精神疾病学习和记忆的疗法的关键。最近的研究提出了一个令人兴奋的想法，即海马体齿状回（DG）中新生成的神经元可能在神经可塑性（包括海马依赖性记忆形成）中发挥作用。成人神经发生发生在生理条件下的哺乳动物大脑（包括成人大脑）的 DG 中，并且新生成的神经元在功能上整合到 DG 中。许多因素，包括抑郁症和其他精神疾病，可能会对海马成人神经发生产生不利影响。相比之下，抗抑郁药治疗和运动（治疗抑郁症的有效方法）可增强 DG 中的成人神经发生。因此，阐明调节成人海马神经发生的基本分子机制，并产生支持成人神经发生在海马依赖性记忆形成中的作用的明确证据，对于心理健康研究来说是一个关键而及时的问题。尽管许多研究评估了成人神经发生在海马依赖性学习和记忆中的作用，但结果并不一致，使得成人神经发生是否有助于海马依赖性记忆形成仍然存在很大争议。该提案将检验以下假设：ERK5 信号传导介导的成人神经发生在某些但不是所有形式的海马依赖性学习和记忆中发挥着关键作用。