INTERLEUKIN-6 IS NOT EXPRESSED IN ACTIVATED MICROGLIA AND IN REACTIVEASTROCYTES IN RESPONSE TO LESION OF RAT BASAL FOREBRAIN CHOLINERGIC SYSTEM AS DEMONSTRATED BY COMBINED IN-SITU HYBRIDIZATION AND IMMUNOCYTOCHEMISTRY

Interleukin-6 may play an essential role in early inflammatory process es as response to degenerating cholinergic cells in the nucleus basali s of Meynert in patients suffering Alzheimer's disease, The cholinergi c immunotoxin, 192IgG-saporin, was applied to produce selective and sp ecific degenerations of basal forebrain cholinergic cells, To disclose the lesion-induced temporal cascade of the expression pattern of IL-6 , and to reveal the cellular source for production and secretion of IL -6 in vivo after endogeneously induced basal forebrain cholinergic cel l loss, both in situ hybridization and immunocytochemistry for IL-6 we re performed, To identify the cell types expressing IL-6 mRNA, double labeling techniques were applied combining in situ hybridization techn ique with immunocytochemistry and lectin histochemistry for both micro -and astroglia and a number of neuronal markers including choline acet yltransferase, parvalbumin, and neurofilaments, In the intact brain, I L-6 is mainly localized in neurons, in particular in both cholinergic and GABAergic neurons of the basal forebrain, Although basal forebrain cholinergic lesion resulted in a dramatic increase in the number of m icro-and astroglial cells at the lesion site, IL-6 expression could no t be detected in any of the lesion-induced activated glial cell types, Moreover, cholinergic lesion led to a reduced number of IL-6-expressi ng cells in the basal forebrain, which is assumed to be due to the los s of cholinergic cells, The predominantly neuronal localization in rat brain suggests a role for IL-6 in activating micro-and astroglial cel ls in response to degenerating cholinergic neurons. (C) 1998 Wiley-Lis s, Inc.