Effect of ellagic acid on BDNF/PI۳K/AKT-mediated signaling pathways in mouse models of depression

Objective(s): The aim of this study is to investigate the possible role of the hippocampal BDNF-PI۳K-AKT signaling pathway in the antidepressant-like activity of ellagic acid (EA) in mice.Materials and Methods: Male BALB/C mice were divided into ۵ groups; vehicle (۰.۱ ml/day), sertraline (۵mg/kg), EA (۱ mg/kg), EA+BKM۱۲۰ (PI۳K inhibitor), EA+MK۲۲۰۶ (AKT inhibitor). EA, sertraline and vehicle were injected intraperitoneally for ۱۴ days. Locomotor activity was determined by open field test. The tail suspension test was used to detect the antidepressant-like effect. After behavioral tests, hippocampal tissue was obtained and Western blot analyzes were performed for BDNF and pAKT۱. Results: Sertraline and EA provided a reduction in immobility time in the tail suspension test when compared with the control group. BKM۱۲۰ and MK۲۲۰۶ administration reversed this effect of EA. No statistical difference was found between groups in terms of locomotor activity. EA treatment caused an increase in hippocampal BDNF and pAKT۱ levels in mice. While inhibitory agent administrations did not affect the increase of BDNF induced by EA, MK۲۲۰۶ administration reversed the increase in pAKT۱ observed with EA.Conclusion: It has shown that EA has an antidepressant-like effect in mice without changing locomotor activity, and this effect may be mediated by the BDNF-PI۳K-AKT signaling pathway.

کلیدواژه ها:

Akt ، BDNF ، Depression ، Ellagic acid ، PI۳K