Tanaka T, Yamada K, Senzaki K, Narimatsu H, Nishimura K, Kameyama T, Nabeshima T
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University School of Medicine, Japan.
Eur J Pharmacol. 1998 Jul 10;352(2-3):135-42. doi: 10.1016/s0014-2999(98)00344-6.
We have reported that the continuous infusion of beta-amyloid protein-(1-40) into the rat cerebral ventricle produces learning and memory deficits accompanied by dysfunction in the cholinergic and dopaminergic systems. L-Pyroglutamyl-L-asparaginyl-L-seryl-L-prolyl-L-arginylglycinamide (NC-1900), an active fragment analog of arginine vasopressin in the rat brain, is a stable peptide with a five-fold longer half-life than that of arginine vasopressin-(4-9). In the present study, we examined the effects of NC-1900 on learning and memory deficits in beta-amyloid protein-(1-40)-infused rats. The rats were injected subcutaneously with NC-1900 (0.1 and 1 ng kg(-1)) once a day throughout the period of behavioral examination. In the beta-amyloid protein-infused rats, learning and memory in water maze and passive avoidance tasks were impaired compared with these in the control rats. NC-1900 prevented the learning and memory deficits in beta-amyloid protein-infused rats. Moreover, NC-1900 tended to increase the choline acetyltransferase activity in the frontal cortex of the beta-amyloid protein-infused rats. These results suggested that NC-1900 could be 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)会导致学习和记忆缺陷,并伴有胆碱能和多巴胺能系统功能障碍。L-焦谷氨酸-L-天冬酰胺-L-丝氨酰-L-脯氨酰-L-精氨酰甘氨酰胺(NC-1900)是大鼠脑中精氨酸加压素的活性片段类似物,是一种稳定的肽,其半衰期比精氨酸加压素(4-9)长五倍。在本研究中,我们研究了NC-1900对β-淀粉样蛋白(1-40)输注大鼠学习和记忆缺陷的影响。在整个行为检查期间,每天给大鼠皮下注射一次NC-1900(0.1和1 ng kg-1)。与对照大鼠相比,β-淀粉样蛋白输注大鼠在水迷宫和被动回避任务中的学习和记忆受损。NC-1900可预防β-淀粉样蛋白输注大鼠的学习和记忆缺陷。此外,NC-1900倾向于增加β-淀粉样蛋白输注大鼠额叶皮质中的胆碱乙酰转移酶活性。这些结果表明,NC-1900可能对治疗阿尔茨海默病患者有用。