Analysis of activated glial cells by glycome abnoumality in lysosomal didease

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Sandhoff disease (SD) is a lysosomal β-hexosaminidase (Hex) deficiency involving excessive accumulation of undegraded substrates, including terminal GlcNAc-oligosaccharides and GM2 ganglioside, and progressive neurodegeneration. In this study, we isolated astrocytes and microglia from the neonatal brain of Sandhoff disease model mice, and demonstrated the abnormalities of SD-glial cells. We found remarkable differences in the cell proliferation of SD astrocyte (ASD) when compared to cells isolated from wild type mice, with a faster growth rate of ASD cells. In addition, we observed increased ERK phosphorylation in ASD cells, but Akt phosphorylation was decreased. These results indicated that the up-regulation of ERK phosphorylation and the increase in proliferation of ASD astrocytes were dependent upon GM2/GA2 accumulation. Furthermore, inhibitors for PKC and Akt reduced the production of MIP-α or by SD-Micoglia. These findings may represent a mechanism in linking activation of glial cells observed in Sandhoff disease.