Microglia Density Decreases with Age in a Mouse Model of Huntington's Disease

Huntington's disease (HD) is characterized by selective neuronal loss and reactive gliosis. In the R6/2 transgenic HD mouse model, there is no selective cell loss, although astrocytosis has been reported. Since there have been no previous studies on microglia in this model, we have undertaken a detailed investigation of microglia in six different forebrain regions in the R6/2 mouse and their wild-type littermates at two time points. Microglia were identified using the histochemical marker isolectin B4 and interactions of genotype, region, and age were analyzed. Results showed that there was a significant decrease in the number of microglia with age in both wild-type and R6/2 brains, which was more pronounced in the transgenic mouse. There were also morphological changes with age observed in both genotypes. As early as 7 weeks of age, structural microglial abnormalities could be seen in R6/2 brains, including bulbous swellings and long stringy processes; comparable changes were seen at 16 weeks in wild-type brains. At 14.5 weeks, microglia in R6/2 mouse brains were smaller in size with condensed nuclei and fragmentation of their processes. We suggest that the density and morphology of microglia change with normal aging and that this process is accelerated in R6/2 brains. Such changes in the dynamic status of microglia may lead to an impairment of their neurosupportive functions. Further studies are needed to understand better the role of microglia in aging and neurodegeneration.