Regulatory role of melatonin in Notch1 signaling pathway in cerebral cortex of Aβ 1−42 -induced Alzheimer’s disease rat model

Background Soluble Amyloid-beta (Aβ) oligomers are thought to play a key role in the pathogenesis of Alzheimer’s disease (AD), which is the most common age-associated neurodegenerative diseases with obvious neuropathological changes and functional decline in both cortical and subcortical regions. Melatonin is ubiquitously distributed and multifunctioning indoleamine. Accumulating studies support that melatonin is potential therapeutic molecule for AD through modulating a broad variety of signaling pathways. In recent years, Notch1 signaling pathway is been known involved in dynamic changes in the cellular architecture and function of adult brain, as well as associated with the pathophysiology of AD and other neurodegenerative disorders. Methods and results In this study, we performed real-time polymerase chain reaction, immunohistochemistry and western blotting analyses using the cerebral cortical tissues of Aβ 1−42 oligomers-induced AD rats with or without melatonin treatment. Our results showed that soluble Aβ 1−42 oligomers decreased the expression of the main components of Notch1 signaling pathway, Notch1, NICD and Hes1 in the cerebral cortex, and melatonin could restore the level of Notch1, NICD and Hes1. Conclusion This observation suggests that targeting of Notch1 signaling might be a promising therapeutic approach for AD and other age-associated neurodegenerative diseases, and melatonin might serve as a potential therapeutic agent for AD and other age-associated neurodegenerative diseases.