Effects of donepezil, an acetylcholinesterase inhibitor, on neurogenesis in a rat model of vascular dementia

To evaluate the effect of donepezil on neurogenesis, we orally treated rats with donepezil (10 mg/kg) once a day for 3 weeks, and injected BrdU over the same 3-week period to label newborn cells. The doses of donepezil that we used have been reported to activate cholinergic activity in rats. After 3 weeks, a water maze task was performed on these rats to test spatial learning, and a subsequent histopathological evaluation was conducted. Donepezil improved memory impairment and increased the number of BrdU-positive cells in the dentate gyrus (DG) of BCCAO animals. These results indicated that donepezil improves cognitive function and enhances the survival of newborn neurons in the DG in our animal model of VaD, possibly by enhancing the expression of choline acetyltransferase and brain-derived neurotropic factor.