Insulin attenuates epileptiform discharge-induced oxidative stress by increasing zinc-α2-glycoprotein in primary cultured cortical neurons

This study investigated the effect and mechanism of insulin on ZAG expression and epileptiform discharge-induced oxidative stress. Primary cultured cortical neurons were treated with insulin, AXL1717 (inhibitor of insulin-like growth factor-1 receptor), or BMS-754807 (inhibitor of both insulin receptor and insulin-like growth factor-1 receptor). Mg2+-free epileptiform discharge model was also made. Levels of ZAG and AZGP1 mRNAs in neurons were measured. Oxidative stress in Mg2+-free-treated treated neurons underwent AZGP1 knock-down, AZGP1 overexpression, or insulin treatment was determined. Insulin treatment increased ZAG expression in neurons; this insulin-induced ZAG increase was abolished by either AXL1717 or BMS-754807. Either insulin treatment or ZAG overexpression suppressed epileptiform discharge-induced oxidative stress in neurons. Knock-down of ZAG abolished the antioxidative stress effect of insulin. Insulin-induced ZAG increase in neurons was mainly related to the activation of insulin-like growth factor-1 receptors. Insulin presented its antioxidative stress effect in neuronal epileptiform discharge models by increasing ZAG.

Source: NeuroReport - April 27, 2019 Category: Neurology Tags: CELLULAR, MOLECULAR AND DEVELOPMENTAL NEUROSCIENCE Source Type: research