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一种基因变异BDNF多态性改变了老鼠和人类的灭绝学习
Fatima Soliman1, Charles E Glatt, Kevin G Bath
1The Sackler Institute for Developmental Psychobiology, Weill Cornell Medical College, New York, NY 10065, USA. fas2002@med.cornell.edu
Science (New York, N.Y.)
|January 16, 2010
概括
大脑衍生神经营养因子 (BDNF) 的常见基因变异影响了小鼠和人类的恐惧灭绝. 这种BDNF等位基因可能会影响焦虑症和治疗疗效,特别是暴露疗法.
科学领域:
- 神经科学是一个神经科学.
- 行为遗传学 行为遗传学
- 精神病学是一个精神病学.
背景情况:
- 鼠标模型对于理解行为中的基因功能至关重要.
- 鼠标模型与人类行为的相关性,特别是关于对焦虑的遗传影响,需要进一步调查.
- 大脑衍生神经营养因子 (BDNF) 基因与焦虑相关的行为有关.
研究的目的:
- 研究BDNF基因中特定的单核酸多态性 (SNP) 在物种间的功能相关性.
- 为了确定携带变异BDNF等位基因的小鼠模型是否可以重复人类与焦虑相关的行为和神经表型.
- 探索这种BDNF变体在焦虑障碍中的潜在作用以及基于灭绝的疗法的有效性.
主要方法:
- 在人类的BDNF基因中识别出一种常见的单核酸多态 (SNP),与焦虑相关的行为有关.
- 创建一种表达变异BDNF等位基因的内科遗传敲入小鼠菌株.
- 在人类和工程小鼠模型中对恐惧条件和恐惧灭绝的表型评估.
- 神经成像 (功能) 检查人类表现出多态的前桃体活动.
主要成果:
- 确定了一种特定的BDNF变体,在小鼠和人类中显示出平行的表型效应.
- 敲入小鼠模型成功地复制了在BDNF多态性的人类中观察到的表型效应.
- 无论是人类还是小鼠,BDNF变异性等位基因都显示条件恐惧反应的灭绝受损.
- 在携带变异BDNF等位基因的人群中观察到非典型的前桃体活性.
结论:
- 鉴定的变异BDNF等位基因在恐惧灭绝学习中发挥着重要作用,影响识别安全线索的能力.
- 这种BDNF变体可能有助于焦虑障碍的病理生理学,焦虑障碍的特点是安全学习的困难.
- 这些发现表明,依赖于灭绝机制的治疗方法,如暴露疗法,可能根据个体的BDNF基因型具有可变的疗效.
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