MEMORY IMPAIRMENT AND NEURAL DYSFUNCTION AFTER CONTINUOUS-INFUSION OFANTI-NERVE GROWTH-FACTOR ANTIBODY INTO THE SEPTUM IN ADULT-RATS

Nerve growth factor is required for the survival and maintenance of ch olinergic neurons in the central nervous system.9,15 The direct infusi on into the rat's septum of an anti-nerve growth factor monoclonal ant ibody, which inhibits nerve growth factor bioactivity seven times more strongly than a polyclonal antibody, caused very severe damage to the hippocampal cholinergic system. Anti-nerve growth factor polyclonal a ntibody also neutralized endogenously occurring nerve growth factor. T he infusion of anti-nerve growth factor polyclonal antibody produced a dysfunction of memory and decreased choline acetyltransferase activit y and acetylcholinesterase staining in the hippocampus. The cholinergi c dysfunction and impairment of memory recovered to the normal level t wo weeks after cessation of the infusion of the anti-nerve growth fact or polyclonal antibody. These results suggest that a deficit of nerve growth factor in the adult brain causes neuronal dysfunction.