Hepatocyte growth factor overexpression in the nervous system enhances learning and memory performance in mice
Hepatocyte growth factor overexpression in the nervous system enhances learning and memory performance in mice
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DOI：
10.1002/jnr.23065
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发表时间：
2012-09-01
影响因子：
4.2
通讯作者：
Nakamura, Toshikazu
中科院分区：
文献类型：
--
作者：
Kato, Takashi;Funakoshi, Hiroshi;Nakamura, Toshikazu
肝细胞生长因子（HGF）及其受体c-Met在发育和疾病状态期间的神经系统中发挥关键作用。然而，HGF在成人脑中的生理作用还不清楚。在本研究中，为了评估其在学习和记忆功能中的作用，我们使用了以神经元特异性方式过表达HGF的转基因小鼠（HGF-Tg）将HGF无损伤地递送到大脑中。与年龄匹配的野生型（WT）对照组相比，HGF-Tg小鼠在Y-迷宫测试中显示出增加的交替率。在Morris水迷宫（MWM）测试中，与WT小鼠相比，HGF-Tg小鼠在第一天找到平台所需的时间更少，而在训练日内逃避到隐藏平台的潜伏期减少。转移试验显示，与WT小鼠相比，HGF-Tg小鼠到达平台确切位置的发生率更高。这些结果表明，HGF的过度表达导致短期和长期记忆的增强。Western blot分析显示，与WT对照组相比，HGF-Tg小鼠海马中N-甲基-D-天冬氨酸（NMDA）受体亚基NR 2A和NR 2B的水平增加，但NR 1没有增加，这表明NR 2A和NR 2B的上调可能代表HGF增强学习和记忆能力的一种机制。这些结果表明，学习和记忆性能的调制是一个重要的生理功能的肝细胞生长因子，有助于正常的中枢神经系统的可塑性，我们建议肝细胞生长因子作为一种新的调节器，更高的大脑功能。(c)2012 Wiley Periodicals，Inc.
Hepatocyte growth factor (HGF) and its receptor, c-Met, play pivotal roles in the nervous system during development and in disease states. However, the physiological roles of HGF in the adult brain are not well understood. In the present study, to assess its role in learning and memory function, we used transgenic mice that overexpress HGF in a neuron-specific manner (HGF-Tg) to deliver HGF into the brain without injury. HGF-Tg mice displayed increased alternation rates in the Y-maze test compared with age-matched wild-type (WT) controls. In the Morris water maze (MWM) test, HGF-Tg mice took less time to find the platform on the first day, whereas the latency to escape to the hidden platform was decreased over training days compared with WT mice. A transfer test revealed that the incidence of arrival at the exact location of the platform was higher for HGF-Tg mice compared with WT mice. These results demonstrate that overexpression of HGF leads to an enhancement of both short- and long-term memory. Western blot analyses revealed that the levels of N-methyl-D-aspartate (NMDA) receptor subunits NR2A and NR2B, but not NR1, were increased in the hippocampus of HGF-Tg mice compared with WT controls, suggesting that an upregulation of NR2A and NR2B could represent one mechanism by which HGF enhances learning and memory performance. These results demonstrate that modulation of learning and memory performance is an important physiological function of HGF that contributes to normal CNS plasticity, and we propose HGF as a novel regulator of higher brain functions. (c) 2012 Wiley Periodicals, Inc.