FGF-2 Reduces Anxiety by Increasing Adult Neurogenesis

FGF-2 通过增加成人神经发生来减少焦虑

• 批准号: 7163140
• 负责人: JAVIER A PEREZ
• 金额: $ 3.24万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7163140
• 关键词: animal developmental psychology; anxiety; behavior test; behavioral /social science research tag; behavioral genetics; dentate gyrus; emotions; experience; fibroblast growth factor; gene environment interaction; gene expression; growth factor receptors; hippocampus; in situ hybridization; laboratory rat; microinjections; neurogenesis; psychological models; psychological stressor; psychopharmacology; receptor expression; socioenvironment; tissue /cell culture

DESCRIPTION (provided by applicant): Recent microarray studies have revealed dysregulation of multiple genes related to the Fibroblast Growth Factor (FGF) family in several brain regions of subjects with a history of major depression, including decreased FGF-2 gene expression in the hippocampus. In the adult human, depression has been linked to reduced hippocampal volume, which may be associated with decreased neurogenesis. In turn the behavioral consequences of depression have been attributed in part to deficits in hippocampal neurogenesis. As genetic background has shown great influence on vulnerability or protection to this or other psychiatric diseases, it is evident that environmental factors pose a great impact on susceptibility for psychiatric illness. While chronic stress leads to increase anxiety and reduced levels of neurogenesis, environmental complexity has been shown to have the opposite effects. This project will investigate the potential role of FGF-2 on experience-dependent neurogenesis and emotional behavior in the rat. We hypothesize that FGF-2 plays a role in reducing anxiety-like behavior by maintaining enhanced levels of neurogenesis in the hippocampus. The Environmental Complexity (EC) model will be used to examine the effects of experience on FGF-2 expression in the adult rat hippocampus. FGF-2 will be administered to determine whether it prevents anxiety and increases neurogenesis in the adult rat, similar to EC. Finally, FGF receptor antagonists will be administered to determine whether the effects of EC on neurogenesis and anxiety are dependent upon FGF- 2 activity in the hippocampus. This work should lead to new discoveries of the molecular and structural mechanisms of how experience influences emotionality, which could help provide novel therapeutic strategies for psychiatric illness.

描述（由申请人提供）：最近的微阵列研究表明，与患有严重抑郁症的受试者的几个大脑区域中，与成纤维细胞生长因子（FGF）家族有关的多个基因失调，包括海马中的FGF-2基因表达降低。在成年人中，抑郁症与海马体积减少有关，这可能与神经发生降低有关。反过来，抑郁症的行为后果部分归因于海马神经发生的缺陷。由于遗传背景对这种或其他精神疾病的脆弱性或保护表现出很大的影响，因此很明显，环境因素对精神病的易感性产生了很大的影响。尽管慢性应激会导致焦虑增加和神经发生水平降低，但环境复杂性已显示出相反的影响。该项目将研究FGF-2对大鼠经验依赖性神经发生和情绪行为的潜在作用。我们假设FGF-2通过维持海马中神经发生水平增强，在减少焦虑样行为中起作用。环境复杂性（EC）模型将用于检查经验对成年大鼠海马中FGF-2表达的影响。 FGF-2将被施用，以确定与EC相似的成年大鼠的焦虑和增加的神经发生。最后，将施用FGF受体拮抗剂，以确定EC对神经发生和焦虑的影响是否取决于海马中的FGF-2活性。这项工作应导致经验如何影响情绪的分子和结构机制的新发现，这可以帮助提供精神病的新型治疗策略。