BDNF prevents central oxidative damage in a chronic unpredictable mild stress model: The possible role of PRDX-1 in anhedonic behavior

•Increased BDNF levels, but no oxidative damage in the hippocampus from animal exposed to the CUMS.•Anhedonic rats show PRDX-1 up-regulation and RELA, ASK-1 and TAK-1 down-regulation.•BDNF and PRDX-1 may have a compensatory role and attenuate oxidative damage. 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.