神经素在杏仁体中分裂EphB2,以控制焦虑
Benjamin K Attwood1, Julie-Myrtille Bourgognon, Satyam Patel
1Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester LE1 9HN, UK.
Nature
|April 22, 2011
概括
神经素蛋白酶调节大脑的可塑性和焦虑. 这项研究揭示了神经素如何控制杏仁体中的EphB2受体动态,影响小鼠的基因表达和焦虑类行为.
科学领域:
- 神经科学是一个神经科学.
- 分子生物学分子生物学
- 行为科学 行为科学
背景情况:
- 暴露于创伤的个体中,很少有百分比会发展出焦虑障碍.
- 关联创伤暴露与焦虑的潜在机制尚不清楚.
- 细胞外蛋白质溶解通过调节神经元可塑性,在恐惧反应中发挥作用.
研究的目的:
- 研究蛋白酶神经素在与压力相关的可塑性和焦虑中的作用.
- 阐明涉及桃体内EphB2-NMDA受体相互作用的分子机制.
- 了解Fkbp5基因表达和焦虑类行为的调节.
主要方法:
- 利用神经素缺乏和野生型小鼠模型.
- 在杏仁体内注射神经素,抗EphB2抗体或Fkbp5基因沉默.
- 分析了EphB2裂变,EphB2-NR1相互作用动态,Fkbp5基因表达和类似焦虑的行为.
主要成果:
- 压力会诱导杏仁体中EphB2的神经素依赖的分裂,使其与NMDA受体分离.
- 这种裂变增强了NMDA受体活性,提高了Fkbp5的调节,并增加了类似焦虑的行为.
- 神经素缺乏防止EphB2裂变,减弱Fkbp5诱导,并减少焦虑.
结论:
- 神经素对老鼠的压力诱导的杏仁体可塑性和类似焦虑的行为至关重要.
- 一个新的途径将杏仁体中压力诱导的EphB2蛋白解与焦虑联系起来.
- 针对这种途径可能为焦虑症提供治疗策略.
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