NEUROTOXICITY OF CHOLESTEROL OXIDES ON CULTURED CEREBELLAR GRANULE CELLS

Cultured rat cerebellar granule cells were used to determine the poten tial neurotoxicity of cholesterol oxides. The cholesterol oxides teste d included: 7-beta-OH-, 7-keto-, 19-OH-, 22(R)-OH-, 22(S)-OH- and 25-O H-cholesterol. Among them, 7-beta-OH- and 7-keto-cholesterol were the most efficacious in causing neuronal death such that 20 mu g/ml (50 mu M) of these agents killed more than 80% of cells in 2 days. 7-beta-OH -cholesterol at this concentration killed 50% of cells in approximatel y 7 h. A number of pharmacological agents were tested for their abilit ies to prevent neuronal death induced by cholesterol oxides. Among the m, aurintricarboxylic acid, vitamin E and methyl-beta-cyclodextrin wer e able to prevent cholesterol oxide-induced neurotoxicity in a dose-de pendent manner. These results suggest that, in addition to causing pat hological changes in cells directly involved in atherosclerosis, chole sterol oxides may induce toxicity in neurons of the central nervous sy stem. (C) 1998 Elsevier Science Ltd. All rights reserved.