Ephrin‐A3 reverse signaling regulates hippocampal neuronal damage and astrocytic glutamate transport after transient global ischemia. (31st July 2014)

• Record Type: Journal Article
• Authors: Yang, Jinshan; Luo, Xiang; Huang, Xiaojiang; Ning, Qin; Xie, Minjie; Wang, Wei
• Is Part Of: Journal of neurochemistry. Volume 131:Number 3(2014:Nov.)
• Page Start: 383
• Page End: 394
• Publication Date: 2014-07-31
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12819
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12819-abs-0001"> <title>Abstract</title> <p>Increasing evidence indicates that the Eph receptors and their ephrin ligands are involved in the regulation of interactions between neurons and astrocytes. Moreover, astrocytic ephrin‐A3 reverse signaling mediated by EphA4 receptors is necessary for controlling the abundance of glial glutamate transporters. However, the role of ephrin‐A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. In the present study, we found that the EphA4 receptor and its ephrin‐A3 ligand, which were distributed in neurons and astrocytes, respectively, in the hippocampus showed a coincident up‐regulation of protein expression in the early stage of ischemia. Application of clustered EphA4 decreased the expressions of astrocytic glutamate transporters together with astrocytic glutamate uptake capacity through activating ephrin‐A3 reverse signaling. In consequence, neuronal loss was aggravated in the CA1 region of the hippocampus accompanied by impaired hippocampus‐dependent spatial memory when clustered EphA4 treatment was administered prior to transient global ischemia. These findings indicate that EphA4‐mediated ephrin‐A3 reverse signaling is a crucial mechanism for astrocytes to control glial glutamate transporters and prevent glutamate excitotoxicity under pathological conditions. <boxed-text content-type="graphic" id="jnc12819-blkfxd-1001" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgh2ck1xq8z" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> <p>Astrocytic ephrin‐A3 reverse signaling mediated by EphA4 receptor is necessary for controlling the abundance of glial glutamate transporters under physiological conditions. However, the role of ephrin‐A3 reverse signaling in astrocytic function and neuronal death under ischemic conditions remains unclear. We found EphA4‐mediated ephrin‐A3 reverse signaling to be a crucial mechanism for astrocytes to control glial glutamate transporters and protect hippocampal neurons from glutamate excitotoxicity under ischemic conditions, this cascade representing a potential therapeutic target for stroke.</p> </abstract>