Investigação de parâmetros bioquímicos em dois modelos animais de depressão induzidos por desamparo aprendido e administração do lipopolissacarideo de E.Coli

Abstract

Major depression has a great impact on an individual’s quality of life and it is considered the leading cause of burden in terms of years lost due to disability. However, despite the severity of depression, the pathophysiology of the disease is still elusive. In this regard, the use of animal models plays an important role in research for the etiology of depression. This work compared biochemical alterations occurring on serum, prefrontal cortex (PFC) and hippocampus in two animal models of depression: learned helplessness and administration of lipopolyssaccharide from E.Coli (LPS). Learned helplessness protocol used in this work resulted in 70 % of helpless mice, assessed by the inability to escape from electroshocks given 24 h or 48 h after the helpless-induction session. The other 30 % of mice were considered resilient. Helpless animals showed more oxidative damage in PFC and serum when compared to controls. No difference was seen between helpless and resilient groups, but there was a positive correlation between the oxidative damage on serum and PFC and helpless behavior. There was no difference in the concentration of IL-1β, TNFα, IL-6 and IL-10 cytokines on PFC and hippocampus of the animals exposed to the learned helplessness test, but there was a significant positive correlation between IL-6 concentration and depressive-like behavior on hippocampus. Indoleamine 2,3-dioxygenase (IDO) enzyme activity was not altered on learned helplessness model. Systemic administration of LPS (0,8 mg/kg) induced sickness behavior on animals characterized by decreased food and water intake, bodyweight loss and altered body temperature 6 h after administration. Sickness behavior is over after 24 h, but LPS-treated mice displayed higher immobility time in the tail suspension test when compared to saline. There was more oxidative damage in serum, PFC and hippocampus of LPS group when compared to saline and controls. No differences on IL-1β and TNFα concentration on serum, PFC and hippocampus of the animals were detected, suggesting a transient nature of the LPS-induced inflammation. LPS-treated group displayed higher concentrations of IL-6 on PFC when compared to saline group, and IL-6 concentration positively correlated to depressive-like behavior. IL-10 concentrations on hippocampus were negatively correlated to depressive-like behavior and IDO activity was increased on PFC and decreased on hippocampus of LPS-treated mice. Data presented here corroborate for the hypothesis of immune activation during depressive episodes, then resulting in oxidative damage assessed in two animal models of depression. IDO activity behaved with some specificity in each animal model depending on the brain or systemic area.