DNA synthesis in Alzheimer type II astrocytosis. The question of astrocytic proliferation and mitosis in experimentally induced hepatic encephalopathy

Abstract

Hepatic encephalopathy is associated with development of Alzheimer type II astrocytosis consisting of large, pale, frequently paired astrocytic nuclei. Previous studies have suggested that the paired forms are a manifestation of astrocytic proliferation and that the two nuclei of paired forms are in separate cells and have an equal (diploid) DNA complement. A model of hepatic encephalopathy can be produced using methionine sulfoximine to inhibit irreversibly the enzyme glutamine synthetase, resulting in elevated brain ammonia levels and development of Alzheimer type II astrocytosis. Using this model Sprague-Dawley rats were simultaneously injected with methionine sulfoximine 300 mg/kg and tritiated thymidine 15 mCi/kg. Autoradiography of cerebral sections from animals killed 18 to 36 hours after the injection revealed many heavily labeled cortical Alzheimer type II astrocytic nuclei. These findings are consistent with DNA synthesis and mitotic division of Alzheimer type II astrocytes.