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 maintenance of cholinergic neurons in the central neuronal system. In senile dementia of the Alzheimer type, learning and memory are impaired by the loss of neurons in the magnocellular cholinergic neuronal system. It is, therefore, of interest to investigate the role of nerve growth factor in senile dementia of the Alzheimer type. We now found that 6-(4-hydroxybutyl)-2,3,5-trimethyl-1,4-benzoquinone (TMQ) stimulates nerve growth factor synthesis in mouse astroglial cells and that the compound has improving effects on memory and choline acetyltransferase activity in basal forebrain-lesioned rats, an amnesia animal model. TMQ ameliorated amnesia in the water maze and passive avoidance tasks. The compound not only restored the reduced choline acetyltransferase activity in the parietal cerebral cortex, but also increased nerve growth factor content and choline acetyltransferase activity in the hippocampus, although it did not change either of these parameters in any brain region in intact rats. These results suggest that the compound activates cholinergic neurons only in the damaged brain and, further, indicate that nerve growth factor stimulators could be used in clinical trials for the treatment of senile dementia of the Alzheimer type.