A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease

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• 作者：Pingping He ; Xinping Ouyang ; Shouhong Zhou ; Weidong Yin ; Chaoke Tang ; Moshe Laudon ; Shaowen Tian
• 关键词：Melatonin ; Neu-P11 ; Memory ; Alzheimer' disease ; Rats
• 刊名：Hormones and Behavior
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：64
• 期：1
• 页码：1-7
• 全文大小：1015 K

文摘

Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against A¦Â-induced injury in vitro and in vivo. Neu-P11 (piromelatine, N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-4-oxo-4H-pyran-2-carboxamide) is a novel melatonin (MT1/MT2) receptor agonist and a serotonin 5-HT1A/1D receptor agonist recently developed for the treatment of insomnia. In the present study we firstly investigated whether Neu-P11 and melatonin enhance memory performance in the novel object recognition (NOR) task in rats, and then assessed whether Neu-P11 and melatonin improve neuronal and cognitive impairment in a rat model of Alzheimer' disease (AD) induced by intrahippocampal A¦Â_(1-42) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24 h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal A¦Â_(1-42) injection resulted in hippocampal cellular loss, as well as decreased learning ability and memory in the Y maze and NOR tasks in rats. Neu-P11 but not melatonin attenuated cellular loss and cognitive impairment in the rat AD model. The current data suggest that Neu-P11 may serve as a novel agent for the treatment of AD.