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REGULATION OF HIPPOCAMPAL NEUROGENESIS BY ANTIDEPRESSANTS

抗抑郁药对海马神经发生的调节

基本信息

批准号：
7914988
负责人：
IRWIN LUCKI
金额：
$ 39.32万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-08 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914988
关键词：
Adult Affect Antidepressive Agents Applications Grants Behavior Behavioral Brain-Derived Neurotrophic Factor C57BL/6 Mouse Chronic Chronic stress Citalopram Corticosterone Disease Emotional Exposure to Flow Cytometry Fluoxetine Functional disorder Genetic Genetic Predisposition to Disease Goals Hippocampus (Brain)Hormones Housing Intraventricular Infusion Investigation Laboratories Lead Major Depressive Disorder Measures Mediator of activation protein Medical Modeling Morbidity - disease rate Mouse Strains Mus Neuronal Plasticity Parahippocampal Gyrus Patients Pharmaceutical Preparations Pharmacology Play Procedures Production Public Health Recovery Regulation Rodent Role Stress Techniques Testing Therapeutic Effect adult neurogenesis dentate gyrus depression depressive symptoms economic impact hypothalamic-pituitary-adrenal axis mouse model neurogenesis neurotrophic factor novel reboxetine resilience response treatment effect

项目摘要

This proposal examines how the regulation of adult neurogenesis produced by repeated antidepressant drug treatment in mice may contribute to behavioral recovery from stress and depression. Major depressive disorder results from convergent underlying genetic predispositons and exposure to environmental stress. Evidence for increases of neurogenesis in the adult dentate gyrus of the hippocampus are a model for changes in neuroplasticity that emerge with chronic treatment with antidepressant drugs and serve as a model for the production of therapeutic effects. Most studies have measured the effects of antidepressants using rodents under routine housing conditions and have ignored the critical role of genetics and stress in contributing to drug treatment effects. We have identified a mouse strain (MRL/MpJ) that shows larger increases in neurogenesis following chronic fluoxetine. Also, the addition of stress hormones augments the effects of fluoxetine on neurogenesis in a nonresponder mouse strain (C57BL/6). The central hypothesis of this grant proposal is that genetic predispositions and stress produce a critical role for revealing the effects of chronic antidepressant treatments on hippocampal neurogenesis. The use of flow cytometry as a technique to measure neurogenesis rapidly developed by this laboratory will enable completion of the large number of studies required for investigation of the pharmacology of neurogenesis. The primary goals of this proposal are: 1) demonstrate the critical role of exposure to corticosterone (CORT) in augmenting responses to chronic treatment with antidepressant drugs on neurogenesis and behavior in a responder and nonresponder mouse strain; 2) show whether environmental stress plays a similar role in causing antidepressant drugs to alter neurogenesis and behavior; and 3) determine whether hippocampal BDNF serves as a mechanism underlying

这一建议探讨了成人神经发生的调节是如何产生的