ORAL-ADMINISTRATION OF PROPENTOFYLLINE, A STIMULATOR OF NERVE GROWTH-FACTOR (NGF) SYNTHESIS, RECOVERS CHOLINERGIC NEURONAL DYSFUNCTION INDUCED BY THE INFUSION OF ANTI-NGF 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 an impa irment of memory and a decrease in choline acetyltransferase (ChAT) an d cholinesterase (ChE) activities in the hippocampus. Propentofylline, a xanthine derivative, has potent stimulatory effects on NGF synthesi s/secretion in mouse astrocytes in vitro. To investigate the pharmacol ogical effects of propentofylline in vivo, we induced amnesia in rats by infusing anti-NGF antibody into the septum for 16 days. One group o f rats was given no further treatment, while the other group was treat ed with propentofylline orally once a day for 19 days, commencing 3 da ys before the implantation of the mini-osmotic pump, and continuing th roughout the period during which the animals performed the behavioral tasks. In the treated amnesic rats, learning and memory in the 3 tasks and ChAT and ChE activity were reduced compared to values in control rats. The administration of propentofylline recovered the decreased le arning capacity and the deficit in cholinergic marker enzyme activity. These results suggest that the use of NGF stimulators may provide a n ew approach to the treatment of dementia.