The Function Role Of Cystatin F In Demyelination Disease

Objective:Study on the effect and its mechanism of cystatin F which is typeâ…¡cystein proteinase inhibitor in the demyelinating diseases in the CNS.Methods: Cystatin F knockout mice (background of C57B6/129) and littermate wild-type mice (background of C57B6/129) were treated 0.2%cuprizone for creating demyelinating model of central nervous system(CNS). C57B6 mice were blank control. PLP immunohistochemistry(IHC) and Black Gold Staining were used to observe the remaining myelin of cystatin F knockout mice and littermate wild-type mice. In order to clarify the mechanism of demylination which was influenced by cystatin F, IHC and in situ hybridization(ISH) were used to analysis the accumulation of microglia/macrophage lineage cells and the expression of cathepsin C in corpus callosum of cystatin F knockout mice and littermate wild-type mice which were treated cuprizone for 2 weeks or 4 weeks.Results:1.After cuprizone treated for 4 weeks, the area ratio of remaining myelin in cystatin F knockout mice and littermate wild-type mice were both less than that in blank control mice, and the area ratio of remaining myelin in cystatin F knockout mice was significantly less than that in littermate wild-type mice.2. After cuprizone treated for 4 weeks, the number of microglia/macrophage lineage cells and the expression of cathepsin C in the corpus callosum were significantly higher than that in littermate wild-type mice.3. After cuprizone treated for 2 weeks, there was no significant difference of the area ratio of remaining myelin between the cystatin F knockout mice and littermate wild-type mice, even though both of them were less than that in blank control mice.4. After cuprizone treated for 2 weeks, compared with the littermate wild-type mice ,the number of microglia/macrophage lineage cells and the expression of cathepsin C in the corpus callosum of cystatin F knockout mice were not significantly different. Conclusions:1. Lack of cystatin F gene aggravates cuprizone induce demyelination.2. The accumulation of microglia/macrophage lineage cells which was induced by upregulated cathepsin C would be involved in aggravated demyelination in cystatin F knockout mice.3. Lack of cystatin F gene does not elevate the susceptivity of oligodendrocyte to the toxicity of cuprizone.4. The expression of cathepsin C was not effected by cystatin F knockout.