Search

Prolonged activation of the hypothalamic-pituitary-adrenal (HPA) axis and sustained increase of glucocorticoids have been evidenced in major depression and are related to changes involving neurotrophins and markers of oxidative stress in response to inflammation. This study aimed to evaluate central measures of brain-derived neurotrophic factor (BDNF), oxidative damage and total antioxidant capacity in rats submitted to chronic unpredictable mild stress (CUMS), as well as to investigate the relationship between BDNF levels and differentially processes. For this purpose, male Wistar rats were submitted to CUMS for six weeks. Based on a sucrose preference test (SPT), the animals were divided into anhedonic or non-anhedonic clusters. Afterwards, forced swim test (FST) and open field test (OFT) were performed, and the animals were euthanized. Brain tissue was collected, followed by quantification of oxidative damage, total antioxidant capacity and BDNF levels. Anhedonic behavior was evidenced in stress-susceptible animals through decreased sucrose preference. No differences were found in FST or OFT results. We observed increased BDNF levels in the hippocampus (HPC) of animals exposed to the CUMS protocol, accompanied by decreased total antioxidant capacity, despite the absence of oxidative damage to lipids and proteins. Moreover, we used a bioinformatics approach to identify proteins involved in oxidative stress and inflammation pathways, which were differentially expressed in anhedonic animals from other studies with similar experimental protocol. expressed proteins (DEP) involved in oxidative stress and inflammatory biological Anhedonic behavior was associated with peroxiredoxin-1 (PRDX-1) up-regulation and down-regulation of proteins involved with apoptotic and inflammation signaling (RELA, ASK-1 and TAK-1) in the HPC. Taken together, these data suggest that BDNF and PRDX-1 might be involved in initial stress response, playing a compensatory role by preventing oxidative damage to lipids and proteins through the modulation of antioxidant defense after CUMS in anhedonic animals., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Stress is implicated in the etiology of major depressive disorder (MDD) and leads to the activation of proinflammatory pathways, which are recognized to induce depressive symptoms. For instance, depression is commonly observed in patients with hepatitis C and cancer under IFN therapy, and high levels of inflammatory cytokines are described in the serum of individuals with MDD - which indicate a multi-system aspect of psychiatric disorders. Thus, we evaluated the effects of a two-hit model of depression on peripheral and CNS inflammatory, neurotrophic, and oxidative stress parameters and behavior. Male Wistar rats were submitted to lipopolysaccharide (LPS) injections, followed by a chronic unpredictable mild stress (CUMS) protocol. Rats exposed to CUMS (CUMS + groups) exhibited reduced body weight, sucrose consumption and preference as well as an increased score of coat state and locomotor behavior. Interestingly, higher IFNγ serum levels were observed in the LPS/CUMS + group, which were further correlated with reduced sucrose consumption. Hypertrophy of adrenal gland was also observed in CUMS+, and splenic hypertrophy was exclusive of LPS-injected animals. Brain-derived neurotrophic factor (BDNF) levels were decreased in the serum of CUMS + animals, while no differences were found in the hippocampus and on lipid peroxidation levels. Besides corroborating the effectiveness of the CUMS model on inducing depressive-like behavior, our findings suggest that the combination of different etiological and pathophysiological components of MDD may provide with a more translational approach. Also, the correlation of increased IFNγ peripheral levels with an anhedonic-like phenotype reinforce the contemporary concept of psychiatric disorders being considered multi-system inflammatory diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)