Ultrastructural Modifi cations in Neurons of the Rat Frontal Cortex Induced by Intoxication by tert-Butyl Methyl Ether

We examined ultrastructural modifications in cortical neurons of the frontal part of the cerebral hemispheres of rats under conditions of chronic intoxication of the animals by tert-butyl methyl ether (TBME). Everyday doses of intrastomachic introductions of TBME in the experimental groups were 0.5, 5, 50, and 500 mg/kg. Within 60 days of the experiment, the animals preserved their viability even in the case of the highest TBME doses, but significant negative structural changes were observed in neocortical neurons under these conditions. A significant part of the mitochondria demonstrated swelling, decreases in the number of the cristae, destruction of the external membrane, and, finally, transformation into vacuoles. The endoplasmic reticulum underwent comparable modifications (dilation and destruction of the cisterns and intense vacuolization). The osmiophilia of the neuronal nuclei increased, and the latter were also deformed; the integrity of the nuclear envelope was disturbed. Other cellular organelles also underwent spatial redistribution and destruction. All these processes led to death of a considerable part of cortical neurons because of intense apoptosis followed by phagocytation of the apoptotic bodies by microgliocytes. The above-described modifications progradiently increased throughout the experiment (up to the 60th day). Their pattern was most dramatic at the highest TBME dose used (500 mg/kg), but the corresponding manifestations were quite obvious (although mild) even at the lowest doses (0.5 and 5 mg/kg). High polymorphism and variability were characteristic features of TBME-induced ultrastructural modifications in the rat frontal cortex. Therefore, TBME, an agent extensively used in industry and transport, which is believed to demonstrate relatively low integral toxicity, exerts powerful negative neurotropic effects on neuronal systems in the cerebral cortex and dramatically intensifies apoptosis in these structures.