title: Propofol inhibits inflammatory cytokine-mediated glutamate uptake dysfunction to alleviate learning/memory impairment in depressed rats undergoing electroconvulsive shock.
abstract: Electroconvulsive therapy (ECT) is an effective treatment for major depression, but can result in memory impairment. Several studies have shown that anesthetic propofol can alleviate the impairment of memory induced by ECT. However, the underlying molecular mechanisms remain unclear. We aimed to investigate the effects of propofol and electroconvulsive shock (ECS, analog of ECT in animals) on hippocampal inflammatory cytokines and glutamate uptake in depressed rats. The chronic unpredictable mild stress (CUMS) procedure was adopted to establish a model of depression. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups with the following assignments (n=12 for each group): group C: control group without treatment; group D: CUMS+sham ECS; group DE: CUMS+ECS; group DP: CUMS+propofol (80 mg/kg, i.p.); group DPE: CUMS+propofol (80 mg/kg, i.p.)+ECS. Sucrose preference test and Morris water maze were used to assess behavioral changes. Hippocampal glutamate levels were measured with high performance liquid chromatography and the expression levels of IL-1β, TNF-α, GLAST and GLT-1 was quantificational analyzed by real time PCR or Western Blotting. The results demonstrated that ECS increased the levels of IL-1β and TNF-α, down-regulated the expression of GLT-1, GLAST expression remains stable, heightened the concentration of glutamate in the hippocampus and aggravated learning and memory impairment of depressed rats. Propofol suppressed IL-1β and TNF-α production, up-regulated the expression of GLT-1, decreased the concentration of glutamate in the hippocampus and attenuated the impairment of learning and memory induced by ECS. Propofol alleviate the learning and memory impairment induced by ECS could be partly attributed to its anti-inflammatory effects. This article is part of a Special Issue entitled Brain and Memory.
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: zhuxianlin8@sohu.com.
authors.forename: Xianlin
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xuechao
authors.initials: X
authors.lastname: Hao
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: ms89011068@163.com.
authors.forename: Su
authors.initials: S
authors.lastname: Min
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xie
authors.affiliation: Department of Anesthesiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000150:complications* / Q000209:etiology; D004195:Disease Models, Animal; D005508:Food Deprivation; D005518:Food Preferences / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000627:therapeutic use*; D007859:Learning Disabilities / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D015742:Propofol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014868:Water Deprivation
chemical_list: D016207:Cytokines; D006993:Hypnotics and Sedatives; D018698:Glutamic Acid; D015742:Propofol
keywords: Cytokines; Electroconvulsive shock; Glutamate transporter; Memory; Propofol