Cunha Carla, Angelucci Andrea, D'Antoni Angela, Dobrossy Mate D, Dunnett Stephen B, Berardi Nicoletta, Brambilla Riccardo
San Raffaele Scientific Institute, Milan, Italy.
Neurobiol Dis. 2009 Mar;33(3):358-68. doi: 10.1016/j.nbd.2008.11.004. Epub 2008 Nov 27.
In this study we analyzed the effect on behavior of a chronic exposure to brain-derived neurotrophic factor (BDNF), by analysing a mouse line overexpressing BDNF under the alphaCaMKII promoter, which drives the transgene expression exclusively to principal neurons of the forebrain. BDNF transgenic mice and their WT littermates were examined with a battery of behavioral tests, in order to evaluate motor coordination, learning, short and long-term memory formation. Our results demonstrate that chronic BDNF overexpression in the central nervous system (CNS) causes learning deficits and short-term memory impairments, both in spatial and instrumental learning tasks. This observation suggests that a widespread increase in BDNF in forebrain networks may result in adverse effects on learning and memory formation.
在本研究中,我们通过分析一种在αCaMKII启动子驱动下过表达脑源性神经营养因子(BDNF)的小鼠品系,来研究长期暴露于BDNF对行为的影响,该启动子可将转基因表达特异性地驱动至前脑的主要神经元。使用一系列行为测试对BDNF转基因小鼠及其野生型同窝小鼠进行检查,以评估运动协调性、学习能力以及短期和长期记忆形成。我们的结果表明,中枢神经系统(CNS)中BDNF的长期过表达会导致空间和工具性学习任务中的学习缺陷和短期记忆障碍。这一观察结果表明,前脑神经网络中BDNF的广泛增加可能会对学习和记忆形成产生不利影响。