Figure 4

Rescue of HexB ^−/− mice from GM ₂ storage has limited effect on neuroinflammation. Targeted rescue of β-hexosaminidase deficiency selectively in the neurons of HexB^−/− mice (A) significantly reduced the number of major histocompatibility complex class II (MHC-II)⁺ and CD45⁺ cells in the brain, but not of glial fibrillary acidic protein (GFAP)⁺ astrocytes. (B) We also observed downregulation in the expression of the tumor necrosis factor α (TNFα) and MHC-II genes, but not of interleukin (IL)-1β, GFAP or cyclo-oxygenase 2 (COX-2) in 4-month-old Thy1-HexB;HexB^−/− mice compared to HexB^−/− littermates. (C) Interestingly, the Thy1-HexB;HexB^−/− mice were characterized by fully rescued neurological phenotype, assessed by rotarod, even in the presence of reactive astrocytes and retained brain inflammation. Caspase-3 levels were evaluated in the brain as a measure of neurodegeneration. ***P <0.001; **P <0.01; *P <0.05.