Essential role of brain-derived neurotrophic factor in adult hippocampal function
Essential role of brain-derived neurotrophic factor in adult hippocampal function
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DOI：
10.1073/pnas.0402141101
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发表时间：
2004-07-20
影响因子：
11.1
通讯作者：
Nestler, EJ
中科院分区：
文献类型：
--
作者：
Monteggia, LM;Barrot, M;Nestler, EJ
脑源性神经营养因子（BDNF）调节神经元的发育和功能。然而，很难辨别它在成人大脑中影响复杂行为的作用。在这里，我们使用一个最近开发的诱导敲除系统，以显示删除BDNF在成年小鼠的广泛前脑区域损害海马依赖性学习和长时程增强。我们使用该系统的诱导性质表明，在早期发展阶段的BDNF的损失导致多动症和更明显的海马依赖性学习缺陷。我们还表明，前脑BDNF的损失减弱的行动，地昔帕明，抗抑郁药，在强迫游泳试验，这表明BDNF的参与抗抑郁疗效。这些结果确立了BDNF在成人中的作用，并证明了这种诱导型敲除系统在研究成人大脑中基因功能方面的优势。
Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here,we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain.