Differential expression of inflammatory mediators in rat microglia cultured from different brain regions

Microglial cells show a rather uniform distribution of cell numbers through out the brain with only minor prevalences in some brain regions. Their in s itu morphologies, however, may vary markedly from elongated forms observed in apposition with neuronal fibers to spherical cell bodies with sometimes extremely elaborated branching. This heterogeneity gave rise to the: hypoth esis that these cells are differentially conditioned by their microenvironm ent and, therefore, also display specific patterns of differential gene exp ression. In this study, microglia were isolated from 2-4 week-old mixed CNS cultures that had been prepared from neonatal rat diencephalon, tegmentum, hippocampus, cerebellum and cerebral cortex, and were investigated 24 h la ter. Messenger RNA levels of proteins involved in crucial immune functions of this cell type (TNF-alpha, CD1, Fc gamma receptor II, and IL-3 receptor beta-subunit) have been determined by semi-quantitative RT-PCR. The results clearly show, that three of these mRNAs (TNF-alpha, CD4, Fc gamma receptor II) are differentially expressed in microglia with hippocampal microglia d isplaying the highest levels of these mRNAs. The data strongly support the notion that the status of microglial gene expression depends on their local ization in brain and on specific interactions with other neural cell types. Consequently, it is hypothesized that their responsiveness to signals aris ing in injury or disease may vary from one brain region to another. (C) 199 9 Elsevier Science B.V. All rights reserved.