Monteggia Lisa M, Barrot Michel, Powell Craig M, Berton Olivier, Galanis Victor, Gemelli Terry, Meuth Sven, Nagy Andreas, Greene Robert W, Nestler Eric J
Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA.
Proc Natl Acad Sci U S A. 2004 Jul 20;101(29):10827-32. doi: 10.1073/pnas.0402141101. Epub 2004 Jul 12.
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.
脑源性神经营养因子（BDNF）调节神经元的发育和功能。然而，一直难以辨别其在成年大脑中对复杂行为的影响作用。在此，我们使用最近开发的诱导型基因敲除系统表明，在成年小鼠广泛的前脑区域删除BDNF会损害海马体依赖的学习和长时程增强。我们利用该系统的诱导特性表明，在发育早期阶段BDNF的缺失会导致多动以及更明显的海马体依赖的学习缺陷。我们还证明，前脑BDNF的缺失会减弱去甲丙咪嗪（一种抗抑郁药）在强迫游泳试验中的作用，这表明BDNF参与了抗抑郁药的疗效。这些结果确定了BDNF在成体中的作用，并证明了这种诱导型基因敲除系统在研究成年大脑基因功能方面的优势。
