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.

中文翻译：

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对阿尔茨海默病小鼠模型进行慢性雷美替胺治疗。


先前的研究报道了褪黑激素对阿尔茨海默病 (AD) 啮齿动物模型的有益作用。本研究评估了雷美替胺（Rozerem，一种褪黑激素受体激动剂）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”）中空间学习和记忆以及神经病理学标志物的影响。老鼠”）。从 3 个月大时开始，每日雷美替胺治疗（约 3 毫克/公斤/天）三个月，并没有改善 AD 小鼠的认知能力（水迷宫）。与野生型对照小鼠相比，AD 小鼠没有表现出任何已知逃生平台位置的证据。 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，表明细胞凋亡。从 3 个月大时开始接受雷美替胺治疗 6 个月，这些神经病理学标志物没有产生任何变化。长期褪黑激素治疗改善 AD 小鼠认知和减轻神经病理学的能力并不能推广到该剂量的雷美替胺。