The effect of castanospermine on embryonic mouse cerebellar neurons in culture

This study examines ultrastructural changes in explants of fetal mouse cerebellum following exposure to castanospermine, an inhibitor of N-linked glycosylation and therefore likely to interfere with cell-cell interactions in the developing nervous system. Explants were grown in castanospermine enriched medium for a period of 10 days and compared with identical explants maintained in control culture medium. Both control and treated explants contained many neurons and numerous synaptic profiles. A detailed analysis of 75 thin sections from each group of explants did however reveal highly significant differences between the two. The castanospermine-treated cells contained smaller numbers of cisternae in each Golgi stack; much larger numbers of secretory vesicles which were also substantially larger in size and four times as many coated vesicles per section as control cells. In addition, at 10 days in culture the first changes in the rough endoplasmic reticulum were observed, with individual profiles of reticulum occasionally associated with large vacuoles. Thus, although cerebellar neurons in culture are able to survive prolonged exposure to castanospermine, there are marked ultrastructural changes in subcellular organelles associated with glycoprotein synthesis, packaging and secretion.