A Comparative Study about the Neuroprotective Effects of DHA-Enriched Phosphatidylserine and EPA-Enriched Phosphatidylserine against Oxidative Damage in Primary Hippocampal Neurons

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 H(2)O(2)/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.