ORAL-ADMINISTRATION OF IDEBENONE INDUCES NERVE GROWTH-FACTOR IN THE BRAIN AND IMPROVES LEARNING AND MEMORY IN BASAL FOREBRAIN-LESIONED RATS

Nerve growth factor plays an important role in the survival and mainte nance of cholinergic neurons in the central neuronal system. In senile dementia of the Alzheimer type, learning and memory are impaired by t he loss of neurons in the magnocellular cholinergic neuronal system. I t is, therefore, of interest to investigate the role of nerve growth f actor in this degenerative disorder. Since nerve growth factor does no t cross the blood-brain barrier and is easily metabolized by peptidase s when administered peripherally, it can be used for medical treatment only when directly injected into the brain. We demonstrate here that the oral administration of idebenone, a potent in vitro nerve growth f actors synthesis stimulator, induced an increase in nerve growth facto r protein and mRNA, and in choline acetyltransferase activity, in basa l forebrain lesioned rats, but not in intact rats. Idebenone also amel iorated the behaviroral deficits in habituation, water maze, and passi ve avoidance tasks in these animals. These results suggest that ideben one stimulated nerve growth factor synthesis in vivo and ameliorates t he behavioral defitics which were accompanied with the recovery of the reduced choline acetyltransferase activity in the basal forebrain-les ioned rats.