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

Abstract

We have reported that the continuous infusion of anti-nerve growth factor (NGF) monoclonal antibody into the septum of rats produces an impairment of memory and a decrease in choline acetyltransferase (ChAT) and cholinesterase (ChE) activities in the hippocampus. Propentofylline, a xanthine derivative, has potent stimulatory effects on NGF synthesis/secretion in mouse astrocytes in vitro. To investigate the pharmacological effects of propentofylline in vivo, we induced amnesia in rats by infusing anti-NGF antibody into the septum for 16 days. One group of rats was given no further treatment, while the other group was treated with propentofylline orally once a day for 19 days, commencing 3 days before the implantation of the mini-osmotic pump, and continuing throughout 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 learning capacity and the deficit in cholinergic marker enzyme activity. These results suggest that the use of NGF stimulators may provide a new approach to the treatment of dementia.