Regional heterogeneity of the astroglial immunoreactive phenotype: Effect of lipopolysaccharide

In order to find out whether the concept of regional heterogeneity in astro cytes also applies to the immunoreactive phenotype, we studied cultured pri mary rat astrocytes originating from five different brain regions (cortex, hippocampus, striatum, septum, and brainstem),We investigated this heteroge neity through the ability of lipopolysaccharide (LPS) to differentially ind uce several parameters that are known to characterize activated astroglia: major histocompatibility complex (MHC) class II and intercellular adhesion molecule (ICAM)-1 expression, nitric oxide (NO) production, synthesis of in terleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha). Under basa l conditions, some of these parameters are already heterogeneic, The presen ce of LPS enhances these differences: expression of MHC class LI increases after a 48-hour incubation with LPS, with brainstem and hippocampus astrocy tes reaching the highest levels; NO production is induced by an LPS incubat ion, with the brainstem showing low NO production levels; septum and striat um instead show higher cytokine (TNF-alpha, IL-6) productions, The baseline expression of ICAM-1 also shows major regional differences, with the brain stem diplaying the highest ICAM-1 expression. Our results demonstrate that the immunoreactive abilities of astrocytes show regional heterogeneities. T his specialization may be implicated in the pathophysiological pathways of several neurodegenerative disorders. (C) 1999 Wiley-Liss, Inc.