EXPERIMENTAL INDUCTION OF CORPORA AMYLACEA-LIKE INCLUSIONS IN RAT ASTROGLIA

Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulat e in the human central nervous system during normal ageing, and to an even greater extent in Alzheimer's disease and other neurodegenerative disorders. They are particularly prominent in subpial and subependyma l regions, and are most commonly located within astrocytes and their p rocesses. We previously demonstrated that human CA share many tinctori al and histochemical properties in common with Gomori-positive cytopla smic granules which accumulate in periventricular astrocytes of the ag eing vertebrate brain and in rat astroglial cultures exposed to the su lphydryl agent, cysteamine (CSH). In the present study, long-term expo sure of neonatal rat astrocyte cultures to CSH resulted in the formati on of large spherical, PAS-positive cytoplasmic inclusions which are h ighly reminiscent of, if not identical to, human CA. As in the case of human CA and Gomori-positive astrocyte granules, the CSH-induced CA-l ilte inclusions exhibit non-enzymatic peroxidase activity and consiste nt immunolabelling with antibodies directed against the mitochondrial protein, sulphite oxidase. Taken together, our findings suggest that p rogressive mitochondrial damage and macroautophagy play an important r ole in the biogenesis of CA (and Gomori-positive granules) in astrocyt es of the ageing periventricular brain.