Striatal oligodendrogliogenesis and neuroblast recruitment are increased in the R6/2 mouse model of Huntington's disease

• Compared to WT mice, R6/2 mice exhibit a two-fold increase in BrdU+ striatal cells.
• The phenotypes of striatal BrdU+ cells were identified using specific markers.
• Overexpression of BDNF in R6/2 mice increased the number of striatal neuroblasts.
• Functional implications of the increase in striatal BrdU+ cells are discussed.

The subventricular zone (SVZ) is one of the two major neurogenic regions in the adult mammalian brain. Its close proximity to the striatum suggests that a cell-based therapeutic strategy for the treatment of Huntington's disease (HD) is possible. To achieve this, it is important to understand how adult cell production, migration and differentiation may be altered in the HD brain. In this study, we quantified the number of adult-born striatal cells and characterized their fate in the R6/2 transgenic mouse model of HD. We found that the number of new striatal cells was approximately two-fold greater in R6/2 vs. wild type mice, while SVZ cell proliferation was not affected. Using cell-type specific markers, we demonstrated that the majority of new striatal cells were mature oligodendrocytes or oligodendroglial precursors that were intrinsic to the striatum. We also detected a significant increase in the number of migrating neuroblasts that appeared to be recruited from the SVZ to the striatum. However, these neuroblasts did not mature into neurons and most were lost between 1 and 2 weeks of cell age. Crossing the R6/2 mice with mice the over-expressing brain-derived neurotrophic factor in the striatum increased the numbers of neuroblasts that survived to 2 weeks, but did not promote their differentiation. Together, our data indicate that the potential treatment of HD based on manipulating endogenous progenitor cells should take into consideration the apparent enhancement in striatal oligodendrogliogenesis and the limited ability of recruited SVZ neuroblasts to survive long-term and differentiate in the diseased striatum.

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