2,5‐hexanedione‐induced intermediate filament aggregates contain ubiquitin‐protein conjugate immunoreactivity and resemble Rosenthal fibres

A number of chronic degenerative disorders including cerebellar astrocytomas and Parkinson's disease are characterized by the presence of cytosolic inclusions which contain intermediate filament (IF) aggregates and ubiquitin-protein conjugate immunoreactivity. In cerebellar astrocytomas these inclusions are known as Rosenthal fibres. 2,5-hexanedione (HD) treatment is known to induce IF aggregates in cells in culture. HD-induced aggregates have therefore been studied as a potential model for the clinical inclusions. Exposure of astrocyte cultures to 2 mM HD for 2 or 4 weeks led to the formation of aggregates of the IFs (glial fibrillary acidic protein and vimentin). The aggregates contained ubiquitin-protein conjugates, which, on electron microscopy appeared to be localized in a peripheral shell. In addition, ubiquitin mRNA levels were found to be elevated approximately threefold by HD treatment. HD-induced inclusions and Rosenthal fibres were found to share a number of features. HD administration, therefore, appears to be a suitable model for the production of pathological inclusions.