title: Chronic ceftriaxone treatment rescues hippocampal memory deficit in AQP4 knockout mice via activation of GLT-1.
abstract: 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.
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: yang_jun_2005@yahoo.com.cn.
authors: Jun
authors: J
authors: Yang
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: china123li@yahoo.cn.
authors: Ming-Xing
authors: MX
authors: Li
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: luoyitj@126.com.
authors: Yi
authors: Y
authors: Luo
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: chentao35790@126.com.
authors: Tao
authors: T
authors: Chen
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: thornyliu@hotmail.com.
authors: Jing
authors: J
authors: Liu
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: funny0707@163.com.
authors: Peng
authors: P
authors: Fang
authors: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China. Electronic address: jiangbo_36020319@sina.com.
authors: Bo
authors: B
authors: Jiang
authors: 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. Electronic address: zlhu916@hotmail.com.
authors: Zhuang-Li
authors: ZL
authors: Hu
authors: 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. Electronic address: jinyou81@yahoo.com.cn.
authors: You
authors: Y
authors: Jin
authors: 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. Electronic address: chenj@mails.tjmu.edu.cn.
authors: Jian-Guo
authors: JG
authors: Chen
authors: 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. Electronic address: wangfang0322@yahoo.com.cn.
authors: Fang
authors: F
authors: Wang
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D051401:Aquaporin 4 / Q000172:deficiency*; D002443:Ceftriaxone / Q000627:therapeutic use*; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000235:genetics / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000235:genetics; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D018683:Excitatory Amino Acid Agents; D027342:Excitatory Amino Acid Transporter 2; C493395:Slc1a2 protein, rat; D002443:Ceftriaxone
keywords: 6-cyano-7- nitroquinoxaline-2, 3-dione; ACSF; AMPA; AQP4; BSA; CNQX; Cef; Ceftriaxone; DG; DL-APV; DL-aminophosphonovaleric acid; EPSCs; GLT-1; HPLC-ECD; KO; LTP; Long-term potentiation; Memory; N-methyl-d-aspartate; NMDA; PBS; PP; PS; TBS; aquaporin-4; artificial cerebrospinal fluid; bovine serum albumin; dentate gyrus; excitatory postsynaptic currents; fEPSP; field excitatory postsynaptic potential; glutamate transporter-1; knockout; long-term potentiation; perforant path; phosphate-buffered saline; population spike; reverse-phase HPLC coupled to electrochemical detection; theta-burst stimulation; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid