Investigating inflammatory responses in a corticosterone‐induced model of depression

Major depressive disorder (MDD) is a prevalent neuropsychiatric condition, affecting approximately 264 million people worldwide. While various hypotheses have been proposed for MDD, the full extent of the neuropathology underlying depression has not yet been elucidated. Nonetheless, evidence suggests that inflammation is a key pathological feature underlying depression, and that inflammation can predispose individuals to developing depression. In this study, we utilised a corticosterone (CORT)-induced model of depression in rats, since elevated glucocorticoids are an important feature of MDD. Using this model, we investigated the inflammatory changes that occur both systemically and in various brain regions, focusing on inflammatory cytokines and various markers of innate immune pathways. Additionally, we administered CORT for different durations to assess how the inflammatory status changes depending on the length of elevated CORT levels.CORT or vehicle (sesame oil) is administered daily via subcutaneous injections to Sprague-Dawley (SD) rats for 14, 21 or 28 days. Afterwards, various tissues samples including liver, kidney, frontal cortex, hippocampus, striatum, thalamus and hypothalamus are collected and processed for qPCR analysis. Additionally, tissue samples from the brain are collected and processed for immunofluorescence staining of GFAP and Iba1.Following 14 days of CORT administration, there are alterations to some of the inflammatory cytokines and markers of the innate immune system assessed in the liver, with no alterations to inflammatory markers in the brain. However, at 21 days there are increases in many of the inflammatory cytokines and innate immune markers assessed in both the liver and the kidney. Additionally, in the brain there are elevated levels of cytokines TNFa and Il1b in the striatum, IL1b in the thalamus and TNFa in the hypothalamus. At 28 days, many of the markers that were altered at 21 days return to baseline in the liver and kidney, though TNFa and IL1b in the kidney and IL1b in the liver remain elevated. Additionally, TNFa is elevated in the frontal cortex and striatum following CORT administration.CORT administration impacts inflammation both in the periphery and in the brain. However, the alterations that occur depend on the duration of CORT administration and the tissue.