NG2-expressing cells (NG2 cells) are ubiquitously distributed throughout the gray and white matter in the central nervous system of adult mammals. NG2 cells can undergo cell division and generate oligodendrocytes and astrocytes as well as neurons even in the adult brain. Recently, it was reported that NG2 cells are involved in the pathogenesis of hydrocephalus during development. Even throughout adulthood, NG2 cells might have a role in maintaining the ventricular system in the central nervous system. However, it remains to be delineated for now. In order to address this hypothesis, we generated transgenic rats expressing herpes simplex virus thymidine kinase (HSVtk) gene under the control of the rat NG2 promoter (rNG2-HSVtk Tg rats).
When ganciclovir (GCV), an antiviral drug, was infused continuously in the lateral ventricle of the adult rNG2-HSVtk Tg rats, the NG2 cells began to disappear at 1 day after the start of infusion and then gradually decreased in surrounding area of the lateral ventricle, including the septum, striatum, and corpus callosum. At 2-3 days after the start of GCV administration, Tg rats showed disappearance of ependymal cells and enlarged lateral ventricle along with a decrease in the number of NG2 cells. These data suggest that NG2 cells play a role in maintaining the structure of ventricular system even in the adult brain. Moreover, GCV-treated rNG2-HSVtk Tg rats showed degeneration of nerve fibers in the septum without the neuronal cell death. This degeneration of neuronal processes was observed following enlargement of the lateral ventricle. Now, we are investigating a functional relationship between enlargement of the lateral ventricle and degeneration of nerve fibers in the septum after the selective ablation of NG2 cells in the adult brain.