College of Food Science and Engineering, Ocean University of China, Qingdao 266404, China.
Laboratory for Marine Drugs and Bioproducts, Pilot National Laboratory for Marine Science and Technology (Qingdao), Qingdao 266237, China.
Mar Drugs. 2023 Jul 19;21(7):410. doi: 10.3390/md21070410.
Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against HO/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3β and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.
累积的氧化应激引起的神经损伤是阿尔茨海默病（AD）的特征和主要机制之一。先前的研究表明，富含二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）的磷脂酰丝氨酸（PS）在预防和减轻 AD 进展方面发挥着重要作用。然而，DHA-PS 和 EPA-PS 是否可以直接保护原代海马神经元免受氧化损伤尚未得到研究。在这里，我们评估了 DHA-PS 和 EPA-PS 对 HO/t-BHP 诱导的氧化损伤的神经保护功能及其可能的机制。结果发现，DHA-PS 和 EPA-PS 可显著改善细胞形态并促进神经网络结构的恢复。进一步的研究表明，它们均能显著减轻氧化应激介导的线粒体功能障碍。EPA-PS 显著抑制 ERK 的磷酸化，从而发挥抗凋亡作用，而 EPA-PS 显著增加了 p-TrkB 和 p-CREB 的蛋白表达，从而发挥神经保护作用。此外，EPA-PS 而非 DHA-PS 通过增加 SYN 的表达来增强突触可塑性，并且两者均能显著降低 p-GSK3β 和 p-Tau 的表达水平。这些结果为使用富含 DHA/EPA 的磷脂治疗神经退行性疾病提供了科学依据，也为相关功能性食品的开发提供了参考。
