Journal
NEUROPHARMACOLOGY
Volume 103, Issue -, Pages 122-133Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2015.12.003
Keywords
Depression; Bacterial translocation; Mitogen-activated protein kinases; DUSPs; Oxidative damage; Transcription factor Nrf2
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Funding
- Instituto de Salud Carlos III through the Plan Nacional de I+D+I [FIS PI10/00123]
- CIBERSAM
- Foundation Mutua Madrilena
- Instituto de Salud Carlos III through the Plan Estatal de I+D+I [FIS PI13/01102]
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Recent studies have suggested that depression is accompanied by an increased Intestinal permeability which would be related to the inflammatory pathophysiology of the disease. This study aimed to evaluate whether experimental depression presents with bacterial translocation that in turn can lead to the TLR-4 in the brain affecting the mitogen-activated protein kinases (MAPK) and antioxidant pathways. Male Wistar rats were exposed to chronic mild stress (CMS) and the intestinal integrity, presence of bacteria in tissues and plasma lipopolysaccharide levels were analyzed. We also studied the expression in the prefrontal cortex of activated forms of MAPK and some of their activation controllers and the effects of CMS on the antioxidant Nrf2 pathway. Our results indicate that after exposure to a CMS protocol there is increased intestinal permeability and bacterial translocation. CMS also increases the expression of the activated form of the MAPK p38 while decreasing the expression of the antioxidant transcription factor Nrf2. The actions of antibiotic administration to prevent bacterial translocation on elements of the MAPK and Nrf2 pathways indicate that the translocated bacteria are playing a role in these effects. In effect, our results propose a role of the translocated bacteria in the pathophysiology of depression through the p38 MAPK pathway which could aggravate the neuroinflammation and the oxidative/nitrosative damage present in this pathology. Moreover, our results reveal that the antioxidant factor Nrf2 and its activators may be involved in the consequences of the CMS on the brain. (C) 2015 Elsevier Ltd. All rights reserved.
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