Yang Jun, Li Ming-Xing, Luo Yi, Chen Tao, Liu Jing, Fang Peng, Jiang Bo, Hu Zhuang-Li, Jin You, Chen Jian-Guo, Wang Fang
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Key Laboratory of Neurological Diseases (HUST), Ministry of Education of China, Wuhan 430030, China; The Key Laboratory for Drug Target Researches and Pharmacodynamic Evaluation of Hubei Province, Wuhan 430030, China.
Neuropharmacology. 2013 Dec;75:213-22. doi: 10.1016/j.neuropharm.2013.08.009. Epub 2013 Aug 22.
Aquaporin-4 (AQP4) is the predominant water channel protein in the mammalian brain, and is mainly expressed in astrocytes. Besides its important role in water transport across the blood-brain barrier, our present study demonstrated that AQP4 deficiency impaired hippocampal long-term potentiation (LTP) and hippocampus-dependent memory formation, accompanied by the increase in extracellular glutamate concentration and N-methyl-d-aspartate (NMDA) receptor-mediated currents in hippocampal dentate gyrus (DG) region. The impairment of LTP and memory formation of AQP4 knockout (KO) mice was mediated by the downregulation of glutamate transporter-1 (GLT-1) expression/function, since it can be rescued by β-lactam antibiotic ceftriaxone (Cef), a potent GLT-1 stimulator. These results suggest that AQP4 functions as the modulator of synaptic plasticity and memory, and chronic Cef treatment rescues hippocampal memory deficit induced by AQP4 knockout.
水通道蛋白4（AQP4）是哺乳动物脑中主要的水通道蛋白，主要表达于星形胶质细胞。除了在跨血脑屏障的水运输中发挥重要作用外，我们目前的研究表明，AQP4缺乏会损害海马体长期增强（LTP）和海马体依赖的记忆形成，同时伴有海马齿状回（DG）区域细胞外谷氨酸浓度和N-甲基-D-天冬氨酸（NMDA）受体介导电流的增加。AQP4基因敲除（KO）小鼠的LTP和记忆形成受损是由谷氨酸转运体-1（GLT-1）表达/功能下调介导的，因为它可以被强效GLT-1刺激剂β-内酰胺抗生素头孢曲松（Cef）挽救。这些结果表明，AQP4作为突触可塑性和记忆的调节因子发挥作用，慢性Cef治疗可挽救由AQP4基因敲除引起的海马体记忆缺陷。
