Altered adult hippocampal neurogenesis in the YAC128 transgenic mouse model of Huntington disease

Perturbations in neurogenesis in the adult brain have been implicated in impaired learning and memory. In the present study, we investigated which stages of the neurogenic process are affected in the transgenic YAC128 mouse model of Huntington disease (HD). Hippocampal neuronal proliferation was altered in the dentate gyrus (DG) of YAC128 mice as compared with wild-type (WT) littermate controls in early symptomatic to end-stage mice. In addition, we detected a significantly lower number of immature neurons in the DG of young, pre-symptomatic YAC128 mice. This decrease in neuronal differentiation persisted through the progression of the disease, and resulted in an overall reduction in the number of new mature neurons in the DG of YAC128 mice. There were no changes in cell proliferation and differentiation in the subventricular zone (SVZ). In this study, we demonstrate decreases in neurogenesis in the DG of YAC128 mice, and these deficits may contribute to the cognitive abnormalities observed in these animals.

Research Highlights► Cell proliferation is altered in the dentate gyrus of YAC128 mice. ► Cell differentiation is decreased in the dentate gyrus of YAC128 mice. ► Adult hippocampal neurogenesis is significantly reduced in YAC128 mice. ► Adult neurogenesis is not affected in the SVZ of YAC128 mice.