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Regulatory role of melatonin in Notch1 signaling pathway in cerebral cortex of Aβ1−42-induced Alzheimer’s disease rat model

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Abstract

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 Aβ1−42 oligomers-induced AD rats with or without melatonin treatment. Our results showed that soluble Aβ1−42 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.

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Funding

This study was supported by the Grants from Climbing Scholars Support Plan of Liaoning Province (2012 to JB), Innovation Team Support Program of Universities in Liaoning Province (No. LT2017018 to JB) and the Principal’s Fund Liaoning Medical University (No. 201310160002 to Pan Wang).

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Authors and Affiliations

  1. Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical University, No. 40, Section 3, Songpo Road, Linghe District, Jinzhou, 121001, Liaoning, People’s Republic of China

    Pan Wang, Shuman Zhang, Chunli Hu, Lili Ren & Jing Bi

Authors
  1. Pan Wang
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  2. Shuman Zhang
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  3. Chunli Hu
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  4. Lili Ren
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  5. Jing Bi
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Contributions

PW contributed to concept/design, acquisition of data, data analysis/interpretation, and drafting of the manuscript. SZ, LLR and CH contributed to acquisition of data and data analysis/interpretation. JB contributed to concept/design, data analysis/interpretation, critical revision of the manuscript, and approval of the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jing Bi.

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The authors declare that they have no conflict interest.

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All experimental procedures were performed in accordance with the guidelines of the Animal Care and Use Committee of Jinzhou Medical University and approved by the Animal Ethics Committee of Jinzhou Medical University.

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Wang, P., Zhang, S., Hu, C. et al. Regulatory role of melatonin in Notch1 signaling pathway in cerebral cortex of Aβ1−42-induced Alzheimer’s disease rat model. Mol Biol Rep 50, 2463–2469 (2023). https://doi.org/10.1007/s11033-022-08213-3

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