Repeated peripheral reelin injections modify hippocampal CD11b + microglia morphology in healthy rats and rats exposed to chronic corticosterone

Depression is a leading cause of disability and is often associated with elevated inflammation and other forms of immune dysfunction. Reelin, a glycoprotein involved in numerous neuropsychiatric disorders, is sensitive to both chronic stress and inflammation. Injection of reelin reverses depression-like symptoms and various neurobiological changes induced by exposure to chronic corticosterone. Our hypothesis is that restoring reelin homeostasis can provide a therapeutic approach for disorders of dysregulated reelin expression. However, the role of reelin and impact of reelin injections on inflammation remains poorly understood – neuropsychiatric disorders of low reelin expression include inflammatory components, but reelin levels are also elevated in several inflammatory conditions. To evaluate whether repeated peripheral injections of recombinant reelin, which induced antidepressant effects, influenced inflammatory states in the hippocampus under chronic stress and non-stressed conditions, we conducted morphological assessment of CD11b-positive cells of the hippocampus in rats exposed to chronic corticosterone that were treated with intravenous reelin. Microglia, the resident macrophages of the brain, undergo various morphological changes during acute and chronic stress and inflammatory conditions which can be indicative of their inflammatory states. Our results indicate reelin injections within the therapeutic range altered hippocampal CD11b positive cell morphology in male rodents under control and chronic corticosterone conditions, although the morphological changes observed fit neither a clear anti- nor pro-inflammatory microglial phenotype.