Li Zhongyi, Liu Huan, Han Wenna, Zhu Siyu, Liu Chunhong
College of Food Science, South China Agricultural University, 483#, Wu-Shan Ave., Tian-He District, Guangzhou, 510642, China.
Guangdong Provincial Key Laboratory of Food Quality and Safety, Guangzhou, 510642, China.
Mol Neurobiol. 2023 May;60(5):2871-2883. doi: 10.1007/s12035-023-03251-9. Epub 2023 Feb 6.
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.
壬基酚（NP）在化学工业中广泛使用；它通过环境污染在生物体内蓄积，并导致学习记忆障碍。烟酰胺单核苷酸（NMN）已被发现对中枢神经相关疾病的治疗有积极作用。本研究旨在探讨NMN对NP诱导的体外学习记忆相关损伤的保护作用，并进一步确定其潜在机制。结果表明，NP诱导PC-12细胞氧化应激并损害胆碱能系统、5-羟色胺（5-HT）系统。NMN通过减轻氧化应激以及对5-HT系统和胆碱能系统的保护作用，在分子水平上减轻NP诱导的学习记忆损伤。50 μM NP组显著降低了烟酰胺腺嘌呤二核苷酸（NAD）含量，沉默信息调节因子1（SIRT1）、过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、核因子E2相关因子2（Nrf2）、单胺氧化酶A（MAOA）、脑源性神经营养因子（BDNF）和磷酸化酪氨酸激酶B（p-TrkB）的相对表达显著下调。NMN与NP共同处理显著降低了氧化应激，改善了5-HT和胆碱能系统的稳态，提高了细胞内NAD含量，并显著上调了SIRT1信号通路蛋白的表达。SIRT1抑制剂降低了SIRT1信号通路相关蛋白的表达，这表明NP对学习记忆的损伤以及NMN的保护作用可能是通过SIRT1介导的PGC-1α/MAOA/BDNF信号通路实现的。总体而言，本研究不仅有助于我们了解NP体外导致学习记忆损伤的毒性机制，而且对进一步探索NMN的保健价值和推动相关功能性食品的开发具有重要参考意义。
