Abstract
Objectives: Human cases of 1-bromopropane (1-BP) toxicity showed ataxic gait and cognitive dysfunction, whereas rat studies showed pyknotic shrinkage in cerebellar Purkinje cells and electrophysiological changes in the hippocampus. The present study investigated the effects of 1-BP on astrocytes and oligodendrocytes in the rat cerebellum and hippocampus to find sensitive markers of central nervous system toxicity. Methods: Forty-eight F344 rats were divided into four equal groups and exposed to 1-BP at 0, 400, 800 and 1,000 ppm for 8 h/day; 7 days/week, for 4 weeks. Nine and three rats per group were used for biochemical and histopathological studies, respectively. Results: Kluver-Barrera staining showed pyknotic shrinkage in the cytoplasm of Purkinje cells and nuclei of granular cells in the cerebellum at 1,000 ppm. Immunohistochemical analysis showed increased length of glial fibrillary acidic protein (GFAP)-positive processes of astrocytes in the cerebellum, hippocampus and dentate gyrus at 800 and 1,000 ppm. The myelin basic protein (MBP) level was lower at 1,000 ppm. The numbers of astrocytes and granular cells per tissue volume increased at 400 ppm or higher. Conclusion: The present study showed that elongation of processes of astrocytes accompanies degeneration of granular cells and Purkinje cells in the cerebellum of the rats exposed to 1-BP. The decrease in MBP and number of oligodendrocytes suggest adverse effects on myelination. The increase in astrocyte population per tissue volume in the cerebellum might be a sensitive marker of 1-BP neurotoxicity, but the underlying mechanism for this change remains elusive.
