McKenna James Timothy, Christie Michael A, Jeffrey Brianne A, McCoy John G, Lee Eunho, Connolly Nina P, Ward Chris P, Strecker Robert E
VA Boston Healthcare System/Harvard Medical School, Brockton, MA 02301-5596, USA.
Arch Ital Biol. 2012 Mar;150(1):5-14. doi: 10.4449/aib.v149i5.1375.
Prior research has reported beneficial effects of melatonin in rodent models of Alzheimer's disease (AD). This study evaluated the effect of ramelteon (Rozerem, a melatonin receptor agonist) on spatial learning & memory and neuropathological markers in a transgenic murine model of AD (the B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mouse strain; hereafter 'AD mice'). Three months of daily ramelteon treatment (~3mg/kg/day), starting at 3 months of age, did not produce an improvement in the cognitive performance of AD mice (water maze). In contrast to wild-type control mice, AD mice did not show any evidence of having learned the location of the escape platform. The cortex and hippocampus of AD mice contained significant quantities of beta-amyloid plaques and PARP-positive (poly ADP ribose polymerase) cells, indicating apoptosis. Six months of ramelteon treatment, starting at 3 months of age, did not produce any change in these neuropathological markers. The ability of long term melatonin treatment to improve cognition and attenuate neuropathology in AD mice did not generalize to this dosage of ramelteon.
先前的研究报道了褪黑素在阿尔茨海默病（AD）啮齿动物模型中的有益作用。本研究评估了雷美替胺（Rozerem，一种褪黑素受体激动剂）对AD转基因小鼠模型（B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J转基因小鼠品系；以下简称“AD小鼠”）空间学习与记忆以及神经病理学标志物的影响。从3月龄开始，每日给予雷美替胺治疗3个月（约3mg/kg/天），并未改善AD小鼠（水迷宫实验）的认知表现。与野生型对照小鼠不同，AD小鼠没有表现出任何已经学会逃生平台位置的迹象。AD小鼠的皮质和海马体含有大量β-淀粉样斑块和PARP阳性（聚ADP核糖聚合酶）细胞，表明存在细胞凋亡。从3月龄开始，给予雷美替胺治疗6个月，这些神经病理学标志物没有发生任何变化。长期给予褪黑素治疗以改善AD小鼠认知并减轻神经病理学改变的能力，并不适用于此剂量的雷美替胺。
