Experimental induction of corpora amylacea-like inclusions in rat astroglia

Corpora amylacea (CA) are glycoproteinaceous inclusions that accumulate 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 subependymal regions, and are most commonly located within astrocytes and their processes. We previously demonstrated that human CA share many tinctorial and histochemical properties in common with Gomori-positive cytoplasmic granules which accumulate in periventricular astrocytes of the ageing vertebrate brain and in rat astroglial cultures exposed to the sulphydryl agent, cysteamine (CSH). In the present study, long-term exposure of neonatal rat astrocyte cultures to CSH resulted in the formation of large spherical, PAS-positive cytoplasmic inclusions which are highly reminiscent of, if not identical to, human CA. As in the case of human CA and Gomori-positive astrocyte granules, the CSH-induced CA-like inclusions exhibit non-enzymatic peroxidase activity and consistent immunolabelling with antibodies directed against the mitochondrial protein, sulphite oxidase. Taken together, our findings suggest that progressive mitochondrial damage and macroautophagy play an important role in the biogenesis of CA (and Gomori-positive granules) in astrocytes of the ageing periventricular brain.