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 selectively and specifically destroys cholinergic cells in rat basal forebrain. Activated microglial cells are known to play an important role in phagocytosis in regions of neuronal loss. To study the immunotoxin-induced phagocytic events in the basal forebrain activated microglial cells were visualized by lectin cytochemistry using Griffonia simplicifolia agglutinin and analyzed by electron microscopy. Three and 7 days following an intracerebro-ventricular injection of 4 microg 192IgG-saporin, increased numbers of activated microglial cells were observed at both survival times, but the number was strikingly increased at day 7 postlesion. Three days after immunotoxin application microglial cells displayed features similar to those of resting microglia. Only translucent vacuole-like hollows were found intracellularly beneath the plasma membrane of microglial cells and in the adjoining extracellular space. Most neurons in the vicinity of microglial cells did not show any signs of degeneration. However, 7 days after injection of the immunotoxin microglial cells revealed different stages of phagocytosis. The majority of microglial cells were localized in perineuronal positions attached by processes to large areas of neuronal soma or dendrites, which in general showed signs of severe degeneration. The present study provides electron microscopic evidence for phagocytic microglial reactions in the rat basal forebrain after cholinergic lesion by 192IgG-saporin.