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 factor (NGF) monoclonal antibody into the septum of rats produces neuronal dysfunction in the cholinergic system. Propentofylline has potent stimulatory effects on NGF synthesis/secretion in mouse astrocytes in vitro. To investigate the pharmacological effects of propentofylline, we used an animal model of dementia in which anti-NGF antibody was infused into the septum for 16 days via a mini-osmotic pump. The rats were treated with propentofylline orally once a day throughout the period during which performance in learning and memory tasks was observed. In the vehicle-treated dementia rats, learning and memory ability and choline acetyltransferase and cholinesterase activity were reduced compared to values in the control rats. The administration of propentofylline prevented the decreased learning capacity and the deficit in cholinergic marker enzyme activities. These results suggest that the use of NGF stimulators may provide a new approach to the treatment of dementia.
Nitta
A
A
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Ogihara
Y
Y
Onishi
J
J
Hasegawa
T
T
Furukawa
S
S
Nabeshima
T
T
D000281:Administration, Intranasal; D000818:Animals; D000897:Anti-Ulcer Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000633:toxicity*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy; D003704:Dementia / Q000517:prevention & control*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000201:enzymology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009300:Nasal Septum; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013268:Stimulation, Chemical; D014970:Xanthines / Q000627:therapeutic use*
D000897:Anti-Ulcer Agents; D000911:Antibodies, Monoclonal; D009414:Nerve Growth Factors; D014970:Xanthines; C032114:propentofylline; D002795:Choline O-Acetyltransferase