Localization of glucocorticoid-induced leucine zipper in the brain and correlation with inflammatory mediators in a transgenic mouse model of Alzheimer's disease.

Chronic stress and stress related pathologies such as major depressive disorder are significant risk factors for Alzheimer's disease and related dementia. Stress induced activation of the hypothalamic pituitary axis upregulate glucocorticoid (GC) secretion. Subsequent GC resistance and lack of GR mediated cellular responses has been associated with increased propensity for neuroinflammation and dementia. Glucocorticoid induced leucine zipper (GILZ) is an anti-inflammatory regulatory protein induced by GC that is constitutively expressed in the brain and has been suggested as a unique quantifier of exposure to stressors. In MDD and other stress disorders, reduced GILZ expression, the pathology has been correlated with reduced GILZ expression. The objective of our study is to determine the expression of GILZ in AD brain and correlate with the inflammatory mediators.Localization and quantitation of GILZ expression in the brain was evaluated in the young (2 months) and adult (6 months) old transgenic 5xFAD and wild type mice by immunohistochemistry and real-time polymerase chain reaction (RT-PCR) respectively. The inflammatory mediators known to be associated with GILZ expression including IL-1β, IL-17, TGF-β and IL-10 was evaluated by enzyme linked immunosorbent assay and RT-PCR.GILZ expression was reduced in the hippocampus, cortex, and cerebellum of 5xFAD mice as compared to that in the brain of wild type mice. The reduced GILZ expression correlated with increased inflammatory cytokines in adult 5xFAD mice.Reduced GILZ expression in the brain could contribute to the sustained inflammation and disease progression in AD.