GFAP+ Astrocyte Association with White Matter Fascicles in the Striatum of a Huntington’s Disease Mouse Model
Huntington’s Disease (HD) is an inherited neurodegenerative disease that is caused by a CAG trinucleotide repeat expansion in the huntingtin (HTT) gene. This mutation produces a dysfunctional protein that aggregates and causes degeneration of GABAergic neurons in the striatum, which is a brain region that contributes to movement and cognition. Neuronal degeneration in the HD striatum is accompanied by increased proliferation and dysfunction of astrocytes also known as astrogliosis. Astrocytes are thought to play a major role in the degenerative process although the mechanisms by which they participate in HD are unclear. Astrocyte populations demonstrate heterogeneity and distinction among subtypes that can be recognized through different gene markers. Recent studies showed different populations expressing GFAP, S100b or GLUL might be differentially altered in HD patients. However, whether different subtypes contribute differently to HD is still unknown. We focused on the astrocyte marker GFAP (glial fibrillary acidic protein), which is thought to be connected to astrocyte reactivity and inflammation. Previous research from our lab using the HD mouse model zQ175 mice showed an increase in the number of GFAP+ astrocytes compared to WT mice, specifically for those localized in the dorsomedial (dm) striatum, a brain region associated with the regulation of motor and goal-directed behaviors. Interestingly, we found that these GFAP+ astrocytes in the dm striatum of HD mice were grouped together in clusters in areas of low HTT aggregate load and in association with white matter fascicles. These findings provide insight into the specific location of GFAP+ astrocytes in HD and may help to determine this subtype’s distinct function.