Efeito tipo antidepressivo da miricitrina e sua relação com a neurogênese adulta em camundongos

Abstract

Depression consists of a multifactorial and complex disease, with differentiated symptoms. In cases of refractory depression resistant to treatment, atypical antipsychotics have been associated with antidepressants, in order to improve the response of patients to treatment. A neurogenic mechanism has been proposed for drugs with antidepressant activity. Myricitrin (MIRI) is a flavonoid extracted from various plants of Eugenia genus and presents an atypical antipsychotic profile. The mechanisms proposed for this therapeutics effects include inhibition of nitric oxide (NO) and protein kinase C (PKC) synthesis. Since the inhibition of NO can also produce antidepressant effect, and the atypical antipsychotics may be used as an antidepressant drug, this study aimed to evaluate the effect of repeated treatment with MIRI in an animal model of predictive antidepressant activity and the influence of this on adult neurogenesis. For this, Balb/C male were treated, intraperitoneally, with MIRI during 21 and/or 28 days respectively. After the repeated treatment the animals were subjected to the open field test and the tail suspension test (TST). At the end of the behavioral tests the animals were sacrificed and their brains were removed for immunohistochemical analysis to detect immunoreactivity of cell markers of proliferation (Ki67), neurogenesis (DCX), survival (BrdU) and differentiation (NeuN and GFAP). The repeated treatment of 21 days was able to decrease the immobility time of the animals in the TST without alteration of locomotor activity. MIRI treatment increased the cell proliferation and the number of doublecortin-positive cells in the subgranular zone of the dentate gyrus in the hippocampus, which indicates an increase in hippocampal neurogenesis. Furthermore, the most of the survival cells were differentiated in neurons. Our data demonstrated that repeated treatment with MIRI resulted in antidepressant-like effect, mediated at least in part, by the generation of new neurons in the hippocampus of mice.