EFFECTS OF ORAL-ADMINISTRATION OF A STIMULATOR FOR NERVE GROWTH-FACTOR SYNTHESIS 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 senile dementia of the Alzheimer type. We now found that -(4- hydroxybutyl)-2,3,5-trimethyl-1,4-benzoquinone (TMQ) stimulates nerve growth factor synthesis in mouse astroglial cells and that the compoun d has improving effects on memory and choline acetyltransferase activi ty in basal forebrain-lesioned rats, an amnesia animal model. TMQ amel iorated amnesia in the water maze and passive avoidance tasks. The com pound not only restored the reduced choline acetyltransferase activity in the parietal cerebral cortex, but also increased nerve growth fact or content and choline acetyltransferase activity in the hippocampus, although it did not change either of these parameters in any brain reg ion in intact rats. These results suggest that the compound activates cholinergic neurons only in the damaged brain and, further, indicate t hat nerve growth factor stimulators could be used in clinical trials f or the treatment of senile dementia of the Alzheimer type.