TOPOLOGICAL DISTRIBUTION OF STRESS HORMONE RECEPTORS GR AND MR IN RAT BRAIN

Stress is considered as a significant risk factor in the development of Alzheimer's disease (AD). It was shown that individuals exposed chronic stress had 2.7-fold increased risk for developing AD. It was also demonstrated that AD patients had increased levels of cortisol - stress hormone- in cerebrospinal fluid, plasma and serum compared to healthy subjects. A study indicated that patients under chronic corticosteroid treatment had decreased hippocampal volume and impaired declarative memory. Stress hormones, cortisol in humans and corticosterone in rodents, exert their effects via both glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Immunocytochemical and in situ hybridization studies have shown that GR has a widespread distribution yet MR has a much more limited distribution throughout the brain. Even though there are a good deal of studies on the brain distributions of corticoid receptors in several organisms, general distribution of these receptors has not been fully characterized in rats. Thus, in this study we aimed to determine the general brain distribution of GR and MR in healthy Sprague-Dawley rats in order to provide preliminary data for our further analysis in stress and AD-like pathology models. In the study, whole brain organotypic slice culture was performed from the brains of Sprague-Dawley rats in post-natal day 7. The brain slices were cultured on semipermeable membranes for 10 days in order to guarantee that endogenously released toxic molecules and reactive astrogliosis are minimized. Then the slices were fixed on DIV10 and immunofluorescence labeling was done. Images were taken with Biotek Lionheart FX Automated Microscope and Gen5 software was used to obtain stitched images. Our results indicate that both GR and MR are abundantly found in neocortex, cingulate cortex, striatum, septal region, basal forebrain region, hippocampus, thalamus and hypothalamic region. This is the first study demonstrates the general brain distribution profile of GR and MR in whole rat brain. Despite that the studies state MR has a limited distribution, our study indicates that both GR and MR are abundantly found almost in all brain regions. (The present work was supported by the Research Fund of Istanbul University, Project no: 25555 and 26263.)