Fig. 4.

Autofluorescent storage material accumulation, astrocytosis, and microglia activation in treated and untreated Ppt1-/- mice. Fluorescent micrographs of autofluorescent storage, GFAP+astrocytes, and CD68+ microglia in the S1BF cortex of WT, Ppt1-/- , phosphocysteamine-treated, AAV-treated, and AAV+phosphocysteamine–treated Ppt1-/- mice. No autofluorescent accumulation or glial activation is present in the WT mice at 7 months of age. Conversely, there are high levels of autofluorescent accumulation in the S1BF cortex of untreated Ppt1-/- mice, which coincides with both astrocyte (GFAP) and microglial (CD68) upregulation. In the inset, note that there is more autofluorescent accumulation within CD68+ cells than GFAP+cells, although the majority of storage material appears to be localized to another cell type, most likely the neurons. The storage material in phosphocysteamine-treated mice appears less than the untreated Ppt1-/- mice, while treatment with phosphocysteamine does not appear to affect GFAP or CD68 levels in the S1BF. Conversely, treatment with either AAVonly or AAV+phosphocysteamine resulted in decreased autofluorescence, GFAP+immunostaining, and CD68+ immunostaining. Scale bar 0100 μm