Aquaporin-4 promotes memory consolidation in Morris water maze
Aquaporin-4 promotes memory consolidation in Morris water maze
复制标题
Aquaporin-4 促进莫里斯水迷宫中的记忆巩固
DOI：
10.1007/s00429-011-0373-2
复制
发表时间：
2013-01-01
影响因子：
3.1
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Fan, Yi;Liu, Mengdi;Hu, Gang
水通道蛋白-4（AQP 4）是脑中含量最丰富的水通道蛋白，在神经胶质细胞的末端--突触周围区域极化。已经假设AQP 4在病理生理状态下调节与神经元活动相关的水和钾通量。然而，AQP 4在生理条件下星形胶质细胞信号转导中的作用尚不清楚。在此，在Morris水迷宫（MWM）中测试AQP 4敲除小鼠和野生型同窝小鼠，其允许研究AQP 4在长期学习和记忆中的作用。与野生型小鼠相比，AQP 4敲除小鼠似乎更容易找到MWM中的平台，但更快地忘记，这表明AQP 4敲除小鼠在MWM中表现出记忆巩固受损。此外，在体内和体外，记忆巩固的缺陷与θ爆发刺激诱导的长时程增强的缺陷有关。此外，AQP 4基因敲除小鼠伴随着成人产生的颗粒细胞纳入空间记忆网络的减少。综上所述，我们的研究结果表明，AQP 4在记忆巩固中起着调节作用。靶向神经胶质AQP 4可能是神经退行性疾病和相关记忆障碍的一种新的治疗策略。
Aquaporin-4 (AQP4), the most abundant aquaporin in the brain, is polarized at the glial end-feet facing peri-synaptic areas. AQP4 has been hypothesized to modulate water and potassium fluxes associated with neuronal activity in pathophysiological states. However, the role of AQP4 in astroglial signaling under physiological conditions is unclear. Herein, AQP4 knockout mice and wild-type littermates were tested in the Morris water maze (MWM), which allows for investigating the role of AQP4 in long-term learning and memory. Compared with wild-type mice, AQP4 knockout mice appeared actually to find the platform more easy, but to forget more quickly, in the MWM, indicating that AQP4 knockout mice exhibited impaired memory consolidation in MWM. Moreover, the deficits of memory consolidations were associated with defects in theta-burst stimulation-induced long-term potentiation both in vivo and in vitro. Furthermore, AQP4 knockout mice were accompanied by a decrease in the incorporation of adult-generated granule cells into spatial memory networks. Taken together, our findings indicate that AQP4 plays a modulatory role in memory consolidation. Targeting glial AQP4 may be a new therapeutic strategy for neurodegenerative disorders and related memory impairment.