Neuroimmunology and Therapeutics

Biography

Biography: Patricia Szot

Abstract

Neuroinflammation is proposed to be an important component in the development of several central nervous system (CNS) disorders including depression, Alzheimer’s disease (AD), Parkinson’s disease (PD), and traumatic brain injury (TBI).  The intra-peritoneal (ip) administration of lipopolysaccharide (LPS) induces peripheral inflammation and neuroinflammation as evident be elevations in blood and brain levels of cytokines.  However, the cellular and anatomical sources of these cytokines are not known. Here, we used in situ hybridization to examine in brain and spleen the sources of cytokine production after 3-injection regime previously shown to elevate cytokine levels in brain and blood.  Administration of LPS significantly increased mRNA expression of interleukin (IL)-6 and -10 in the spleen, an important organ for an immune response, consistent with increases in blood levels for these cytokines after LPS.  LPS significantly decreased IL-6 receptor (-6R) mRNA in the spleen, but had no effect on IL-7 or IL-7R mRNA.  In the CNS, IL-6 mRNA was expressed in neurons prior to LPS in regions that include the cortex, cerebellum and hippocampus.  After LPS, IL-6 mRNA expression in these neuronal populations was unchanged, but a diffuse non-neuronal pattern appeared throughout the brain.  IL-6R mRNA showed a pattern of expression similar to IL-6 mRNA and LPS significantly elevated all regions, except cerebellum, mainly in animals which expressed the non-neuronal IL-6 mRNA after LPS.  IL-10 mRNA was widely expressed in neurons in many discrete brain regions, with LPS tending to decrease expression in forebrain regions and increase it in hindbrain regions.  IL-7 and IL-7R had limited expression mainly to the cerebellum.  LPS had no effect on IL-7 or IL-7R mRNA in the CNS.  These studies indicate that LPS induced neuroinflammation has unique effects on regional and cellular patterns in the CNBS and splenic cytokine expression.  It is apparent that LPS can affect neuronal and non-neuronal cells in the brain, with IL-6 demonstrating the greatest change.