Brain glutamic acid decarboxylase-67kDa alterations induced by magnesium treatment in olfactory bulbectomy and chronic mild stress models in rats.

Abstract

The preclinical results indicate that magnesium, an N-methyl-d-aspartate receptor (NMDAR) blocker has anxiolytic and antidepressant-like activity. One of the mechanisms involved in these activities is modulation of glutamate, γ-aminobutyric acid (GABA) system. Based on this, the aim of the present study was to investigate the effect of magnesium on the level of glutamic acid decarboxylase-67kDa (GAD-67) in the different brain areas in the chronic mild stress (CMS) and olfactory bulbectomy (OB) models of depression in rats. Magnesium (15mg/kg) was administered intraperitonealy once daily for 14 days in the OB model and for 35 days in the CMS model. 24h after the last dose, the prefrontal cortex (PFC), hippocampus and amygdala were collected and the GAD-67 protein level was determined by the western blotting method. In the OB model, chronic magnesium treatment normalized decreased by OB protein level of GAD-67 in PFC. CMS did not influence the GAD-67 protein level, however magnesium increased GAD-67 protein expression in amygdala and PFC of stress rats when compared to vehicle-treated stress group. OB or CMS models as well as magnesium treatment did not affect GAD-67 protein level in the hippocampus. Obtained results indicate that the antidepressant-like activity of magnesium in CMS and OB models of depression is associated with an enhanced expression of GAD-67 in the PFC and amygdala.