ELECTRON-MICROSCOPIC EVIDENCE FOR MICROGLIAL PHAGOCYTIC-ACTIVITY AND CHOLINERGIC CELL-DEATH AFTER ADMINISTRATION OF THE IMMUNOTOXIN 192IGG-SAPORIN IN RAT

192IgG-saporin represents a novel cholinergic immunotoxin which select ively and specifically destroys cholinergic cells in rat basal forebra in, Activated microglial cells are known to play an important role in phagocytosis in regions of neuronal loss, To study the immunotoxin-ind uced phagocytic events in the basal forebrain activated microglial cel ls were visualized by lectin cytochemistry using Griffonia simplicifol ia agglutinin and analyzed by electron microscopy, Three and 7 days fo llowing an intracerebro-ventricular injection of 4 mu g 192IgG-saporin , increased numbers of activated microglial cells mere observed at bot h survival times, but the number was strikingly increased at day 7 pos tlesion. Three days after immunotoxin application microglial cells dis played features similar to those of resting microglia, Only translucen t vacuole-like hollows were found intracellularly beneath the plasma m embrane of microglial cells and in the adjoining extracellular space, Most neurons in the vicinity of microglial cells did not show any sign s of degeneration, However, 7 days after injection of the immunotoxin microglial cells revealed different stages of phagocytosis. The majori ty of microglial cells were localized in perineuronal positions attach ed by processes to large areas of neuronal soma or dendrites, which in general showed signs of severe degeneration, The present study provid es electron microscopic evidence for phagocytic microglial reactions i n the rat basal forebrain after cholinergic lesion by 192IgG-saporin. (C) 1997 Wiley-Liss, Inc.