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

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.

Keywords: Learning memory; Nicotinamide mononucleotide; Nonylphenol.