title: A novel melatonin agonist Neu-P11 facilitates memory performance and improves cognitive impairment in a rat model of Alzheimer' disease.
abstract: Previous studies have shown that melatonin is implicated in modulating learning and memory processing. Melatonin also exerts neuroprotective activities against Aβ-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 Aβ(1-42) injection. The results showed that a single morning or afternoon administration of Neu-P11 enhanced object recognition memory measured at 4 or 24h after training. Melatonin was effective in the memory facilitating effects only when administered in the afternoon. Further results showed that intrahippocampal Aβ(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.
authors: Nursing School, University of South China, Hengyang, Hunan, China.
authors: Pingping
authors: P
authors: He
authors: Xinping
authors: X
authors: Ouyang
authors: Shouhong
authors: S
authors: Zhou
authors: Weidong
authors: W
authors: Yin
authors: Chaoke
authors: C
authors: Tang
authors: Moshe
authors: M
authors: Laudon
authors: Shaowen
authors: S
authors: Tian
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D003072:Cognition Disorders / Q000188:drug therapy* / Q000523:psychology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008550:Melatonin / Q000819:agonists*; D008568:Memory / Q000187:drug effects*; D010446:Peptide Fragments / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects*; D011714:Pyrans / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects
chemical_list: D016229:Amyloid beta-Peptides; D007211:Indoles; D010446:Peptide Fragments; D011714:Pyrans; C075222:amyloid beta-protein (1-42); D008550:Melatonin; C581609:N-(2-(5-methoxy-indol-3-yl)-ethyl)-4-oxo-4H-pyran-2-carboxamide