Neurogenesis and progenitor cell distribution in the subgranular zone and subventricular zone of the adult sheep brain.

Progenitor cell proliferation is ubiquitous in the subventricular zone (SVZ) and subgranular zone (SGZ) of adult mammalian brains, however, the abundance and distribution of proliferation are surprisingly heterogeneous between species. In rodents, proliferation is high in both the SVZ and SGZ, while in humans proliferation is prominent in the SVZ but limited in the SGZ. To accurately study proliferation and how it changes in human disease, we should focus on animals in which the patterns of proliferation are consistent with the human brain. In this study, we characterized the neurogenic niches of the adult sheep, an animal model with a longer lifespan than rodents and a highly gyrencephalic brain, using 5-bromo-2'-deoxyuridine (BrdU) as a mitotic marker and neuronal nuclear antigen to identify neuronal lineage cells. Our study demonstrates that the sheep SVZ is organized into the same distinct layers that are comparable to what has been described in humans. The rate of maturation of new neurons was slower in sheep than in previous reports in rodents, with only 20% of BrdU-positive cells showing neuronal phenotype after 4 months survival following BrdU administration. Most importantly, as in the human, there was much greater proliferation in the sheep SVZ than in the SGZ. These results suggest that the sheep is a better basis for comparisons with human SVZ and SGZ neurogenesis than rodents.

No change in progenitor cell proliferation in the hippocampus in Huntington's disease.

Increases in cell proliferation in the hippocampus have been robustly demonstrated in animal models of neurodegenerative diseases like Huntington's disease (HD). However, in the subventricular zone, animal models of HD have demonstrated no change in cell proliferation compared to wild types, while in humans there is a distinct increase in cell proliferation in HD cases. Interestingly, there have been no reports on cell proliferation in the human subgranular zone (SGZ) of the hippocampus in HD, despite numerous transgenic mouse models of HD showing decreased proliferation in the SGZ. Furthermore, HD can be divided into those with mainly mood and mainly motor symptomatology. We hypothesized that HD cases with mainly mood symptomatology would show a greater change in hippocampal proliferation, which has previously been implicated in mood disorders such as depression. Therefore, in the current study we examined and compared proliferation in the SGZ in normal vs. HD, HD mood, and HD motor affected cases. However, our results revealed no significant differences in SGZ proliferation between normal and HD cases, and no differences when divided into groups based on mood and motor symptomatology. Our results were confirmed using a range of cell-cycle protein markers and, overall, were comparable with previous studies of the human hippocampus, where very little proliferation was detected in the adult SGZ. These results demonstrate that in humans the SGZ is far less proliferative than the SVZ, and suggests that hippocampal plasticity in humans does not primarily involve cell proliferation.