Immunohistochemical characterization of neural stem cells in brains of adult brachycephalic dogs in comparison with canine oligodendroglioma cells

Brachycephalic dogs, characterized by unique dome-shaped skulls and limited cerebral cortical volumes, are predisposed to brain tumors, particularly oligodendrogliomas. Canine oligodendrogliomas often arise adjacent to the cerebral ventricles and express several neural stem cell (NSC) markers, including sex-determining region Y-box transcription factor (SOX) 2, suggesting that NSCs are their origin. To investigate why oligodendrogliomas are more prevalent in brachycephalic dogs, the quantity, immunophenotypes, and proliferative activity of NSCs were examined and compared in the brains of adult brachycephalic and non-brachycephalic dogs. Histological examinations revealed clusters of two types of cells, small round cells and medium-sized spindle cells, in the subventricular zone and caudate nucleus in all samples. Immunohistochemically, small round cells were positive for SOX2 and doublecortin, corresponding to type A NSCs (neuroblasts). Medium-sized spindle cells were positive for SOX2, SOX9, and vimentin, corresponding to type B NSCs (multipotent astrocytes). The number of SOX2-positive and proliferating cell nuclear antigen-positive cells in the caudate nucleus was significantly higher in brachycephalic dogs than in non-brachycephalic dogs. We then examined canine oligodendroglioma tissues and found that tumor cells were immunopositive for SOX2, SOX9, and vimentin, similar to the immunophenotype of type B NSCs. These results indicate that brachycephalic adult dogs retain a higher number of NSCs with higher proliferative activity in the brain, which may create an environment prone to oligodendroglioma.