Ultrastructural study of methionine sulfoximine induced Alzheimer type II astrocytosis

Because methionine sulfoximine (MSO), unlike most convulsant drugs, has a long latent period, it can be used to study changes in the brain before the occurrence of seizures. A previous light microscopic study during the preictal period following MSO revealed the development of an Alzheimer type II astrocyte change as the principal morphologic alteration. This ultrastructural study of the brain cortex was performed in rats during the preictal period following MSO administration. The morphologic changes were restricted to the astrocytes and consisted of cytoplasmic enlargement, mitochondrial and rough endoplasmic reticulum proliferation, accumulation of glycogen, development of cisternal and saccular smooth endoplasmic reticulum, nuclear chromatin clumping, and hydropic degenerative changes. These findings resemble those seen in experimental ammonia encephalopathy, suggesting an important role of ammonia in the evolution of the morphologic changes described. The findings, moreover, suggest that the primary effect of MSO is on astrocytes and that astrocytic abnormalities play a role in the development of MSO-induced seizures.