A putative role for calpain in demyelination associated with optic neuritis

Calcium activated neutral proteinase (calpain) is an endopeptidase present in the central nervous system which degrades myelin proteins. To examine th e role of calpain in demyelination associated with optic neuritis, immunocy tochemical expression of calpain was evaluated in Lewis rats with experimen tal optic neuritis. Calpain expression was increased in activated microglia , infiltrating macrophages, activated T cells, and reactive astrocytes in e xperimental optic neuritis compared to controls. Calpain activity and trans lational expression were also examined by Western blotting studies measurin g the extent of myelin protein degradation, calpain-specific fodrin proteol ysis, axonal neurofilament degradation, and calpain proenzyme content. Resu lts showed myelin associated glycoprotein and 68 kD neurofilament protein l evels were significantly decreased while calpain translational expression a nd calpain-autolyzed fodrin levels were significantly increased in experime ntal optic neuritis compared to controls. Thus, increased activity and tran slational expression of calpain in optic neuritis may be integral to the pa thogenesis of this disorder.