Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, Jiangsu, China.
Brain Struct Funct. 2013 Jan;218(1):39-50. doi: 10.1007/s00429-011-0373-2. Epub 2011 Dec 23.
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.
水通道蛋白-4（AQP4）是脑内最丰富的水通道蛋白，在神经胶质终足处呈极化分布，面向突触周围区域。AQP4 被假设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，AQP4 在生理条件下对星形胶质细胞信号的作用尚不清楚。在此，我们在 Morris 水迷宫（MWM）中对 AQP4 敲除小鼠和野生型同窝仔鼠进行了测试，该测试允许研究 AQP4 在长期学习和记忆中的作用。与野生型小鼠相比，AQP4 敲除小鼠实际上在 MWM 中更容易找到平台，但遗忘速度更快，这表明 AQP4 敲除小鼠在 MWM 中表现出记忆巩固受损。此外，记忆巩固的缺陷与体内和体外的 theta 爆发刺激诱导的长时程增强相关缺陷有关。此外，AQP4 敲除小鼠伴随着成年产生的颗粒细胞整合到空间记忆网络的减少。总之，我们的研究结果表明，AQP4 在记忆巩固中发挥调节作用。靶向神经胶质 AQP4 可能是神经退行性疾病和相关记忆障碍的新治疗策略。
