Yamada K, Tanaka T, Senzaki K, Kameyama T, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1998 May 15;349(1):15-22. doi: 10.1016/s0014-2999(98)00166-6.
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.
我们曾报道，向大鼠脑室持续输注β-淀粉样蛋白（1-40）会导致大鼠出现学习和记忆缺陷。丙戊茶碱在体外对小鼠星形胶质细胞中神经生长因子（NGF）的合成/分泌具有强大的刺激作用，并能增加老年大鼠脑内NGF的含量。在本研究中，我们检测了丙戊茶碱对输注β-淀粉样蛋白的大鼠学习和记忆缺陷的影响。在整个行为学检测期间，大鼠每天口服一次丙戊茶碱。与假手术大鼠相比，输注β-淀粉样蛋白的大鼠在Y迷宫中的自发交替行为、在水迷宫和被动回避任务中的表现均显著受损。丙戊茶碱可预防这些行为缺陷，但并未改变输注β-淀粉样蛋白的大鼠海马中胆碱乙酰转移酶活性的降低。这些结果表明，丙戊茶碱对阿尔茨海默病患者的治疗有用。
