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NMN Alleviates NP-Induced Learning and Memory Impairment Through SIRT1 Pathway in PC-12 Cell

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Abstract

Nonylphenol (NP) is widely used in the chemical industry; it accumulates in organisms through environmental contamination and causes learning memory impairment. Nicotinamide mononucleotide (NMN) has been found to have a positive effect on the treatment of central nervous-related diseases. This study aimed to investigate the protective effect of NMN on NP-induced learning memory-related impairment in vitro and to further identify the underlying mechanisms. The results showed that NP induced oxidative stress and impaired the cholinergic system, 5-HT system in PC-12 cells. NMN alleviated NP-induced learning and memory impairment at the molecular level through alleviating oxidative stress and protective effects on the 5-HT system and cholinergic system. The 50 μM NP group significantly reduced the NAD+ content, and the relative expression of SIRT1, PGC-1α, Nrf2, MAOA, BDNF, and p-TrkB were significantly downregulated. Co-treatment of NMN with NP significantly reduced oxidative stress, improved the homeostasis of 5-HT and cholinergic system, enhanced the intracellular NAD+ content, and significantly upregulated the expression of SIRT1 pathway proteins. SIRT1 inhibitors reduced the expression of SIRT1 pathway-related proteins, which implied the impairment of learning and memory by NP and the protective effect of NMN might be achieved through the SIRT1-mediated PGC-1α/MAOA/BDNF signaling pathway. Overall, this study not only help us to understand the toxic mechanism of NP on learning memory impairment in vitro, but also have important reference significance to further explore the health care value of NMN and promote the development of related functional foods.

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Data Availability

All data generated during this study are available from the corresponding author on reasonable request.

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Acknowledgements

We appreciate the contribution of all the members participating in this study.

Funding

This study was supported by the Natural Science Foundation of Guangdong Province (2021A1515010825), Guangdong Key R&D Program, Department of Science and Technology of Guangdong Province (2019B020210002), Generic Technique Innovation Team Construction of Modern Agriculture of Guangdong Province (2021KJ130), and Guangdong Provincial Key Laboratory of Food Quality and Safety (2020B1212060059).

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Authors and Affiliations

  1. College of Food Science, South China Agricultural University, 483#, Wu-Shan Ave., Tian-He District, Guangzhou, 510642, China

    Zhongyi Li, Huan Liu, Wenna Han, Siyu Zhu & Chunhong Liu

  2. Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou, 510642, China

    Zhongyi Li, Huan Liu, Wenna Han, Siyu Zhu & Chunhong Liu

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  1. Zhongyi Li
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  2. Huan Liu
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Contributions

Zhongyi Li: design and conduct of the cell cultural experiments, analysis of the data, and writing the manuscript.

Huan Liu: conduct the Western blotting experiments.

Wenna Han: conduct the cell cultural experiments, and analysis of the relevant data.

Siyu Zhu: conceptualization, writing-review and editing, and funding acquisition.

Chunhong Liu: supervision and funding acquisition.

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Correspondence to Chunhong Liu.

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Li, Z., Liu, H., Han, W. et al. NMN Alleviates NP-Induced Learning and Memory Impairment Through SIRT1 Pathway in PC-12 Cell. Mol Neurobiol 60, 2871–2883 (2023). https://doi.org/10.1007/s12035-023-03251-9

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