PROPENTOFYLLINE PREVENTS NEURONAL DYSFUNCTION INDUCED BY INFUSION OF ANTI-NERVE GROWTH-FACTOR ANTIBODY INTO THE RAT SEPTUM

We have reported that the continuous infusion of anti-nerve growth fac tor (NGF) monoclonal antibody into the septum of rats produces neurona l dysfunction in the cholinergic system. Propentofylline has potent st imulatory effects on NGF synthesis/secretion in mouse astrocytes in vi tro. To investigate the pharmacological effects of propentofylline, we used an animal model of dementia in which anti-NGF antibody was infus ed into the septum for 16 days via a mini-osmotic pump. The rats were treated with propentofylline orally once a day throughout the period d uring which performance in learning and memory tasks was observed. In the vehicle-treated dementia rats, learning and memory ability and cho line acetyltransferase and cholinesterase activity were reduced compar ed to values in the control rats. The administration of propentofyllin e prevented the decreased learning capacity and the deficit in choline rgic marker enzyme activities. These results suggest that the use of N GF stimulators may provide a new approach to the treatment of dementia .