Oral administration of ngf synthesis stimulators recovers reduced brain ngf content in aged rats and cognitive dysfunction in basal-forebrain-lesioned rats

Nerve growth factor (NGF) plays an important role in the survival and maintenance of cholinergic neurons in the central neuronal system. Since this factor does not cross the blood- brain barrier and is easily metabolized by peptidases when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We report here that repeated oral administration of the stimulators for the NGF synthesis, idebenone and propentofylline, produced a significant recovery of the reduced NGF content in the frontal and parietal cortices of aged rats. These compounds also improved deficits of performance in water maze, passive avoidance and habituation tasks in basal-forebrain-lesioned rats. These results suggest that the use of the stimulators for the NGF synthesis may provide a therapeutic approach to cholinergic dysfunction.