Propentofylline improves learning and memory deficits in rats induced by beta-amyloid protein-(1-40).
We have reported that continuous infusion of beta-amyloid protein-(1-40) into the cerebral ventricle produces learning and memory deficits in rats. Propentofylline has potent stimulatory effects on nerve growth factor (NGF) synthesis/secretion in mouse astrocytes in vitro and increases cerebral NGF content in aged rats. In the present study, we examined the effects of propentofylline on learning and memory deficits in beta-amyloid protein-infused rats. The rats were given propentofylline orally once a day throughout the period of behavioral examination. In the beta-amyloid protein-infused rats, spontaneous alternation behavior in a Y-maze, and performance in water maze and passive avoidance tasks were significantly impaired compared to sham-operated rats. Propentofylline prevented these behavioral deficits, but did not change the reduction of the activity of choline acetyltransferase in the hippocampus in the beta-amyloid protein-infused rats. These results suggest that propentofylline is useful for the treatment of patients with Alzheimer's disease.
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
K
K
Yamada
T
T
Tanaka
K
K
Senzaki
T
T
Kameyama
T
T
Nabeshima
D000284:Administration, Oral; D016229:Amyloid beta-Peptides / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D007276:Injections, Intraventricular; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D018697:Nootropic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000008:administration & dosage / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D018697:Nootropic Agents; D010446:Peptide Fragments; D014970:Xanthines; C078592:amyloid beta-protein (1-40); C032114:propentofylline; D002795:Choline O-Acetyltransferase