Modulação da AKT/GSK3-B e SNAP-25 pela administração de curcumina em modelo de mania induzido por cetamina

Abstract

Bipolar disorder is a psychiatric illness associated with alternate states of depression and mania/hypomania episodes. Glycogen synthase kinase 3β (GSK-3β) and synaptosomal-associated protein 25 (SNAP-25) are associated respectively, with the modulation of gene expression and neural plasticity in the pathogenesis of mood disorders. Curcumin, active compound extracted from Curcuma longa, has been described as a neuroprotective agent in neurodegenerative disorders, although their mechanisms of action are not completely elucidated. In this study we investigate the impact of ketamine-induced model of mania on GSK-3β and SNAP-25 immunocontent, and assess in this model the neuroprotective effect of Curcumin pretreatment. Rats received peanut oil (vehicle), curcumin 20 or 50 mg/kg (p.o.), once a day for 14 days. From the 8th to the 14th day the animals also received saline or ketamine (25 mg/kg i.p.), once a day. On the 15th day of treatment, the animals received a single injection of ketamine or saline and the locomotor activity was assessed in the open-field apparatus after 30 min. Immunodetection of the proteins pGSK-3β and SNAP-25 were evaluated by Western Blotting in the prefrontal cortex (PFC) and the hippocampus (HP). The administration of Curcumin in doses of 20 and 50 mg/kg prevented the hyperlocomotion induced by ketamine in the open-field test. In addition, both doses of Curcumin prevented the decrease in density of pGSK-3β and SNAP-25 ketamine-induced in PFC and HP. In conclusion, our results show that Curcumin prevents hyperlocomotion and presents a neuroprotective effect by restoring SNAP-25 density probably via modulation of GSK-3β.