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

Abstract

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 H2O2/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.

Transcriptomic atlas of midbrain dopamine neurons uncovers differential vulnerability in a Parkinsonism lesion model

“…Nos1ap , nitric oxide synthase 1 adaptor protein, may play a role in excitotoxic neuronal damage in neurodegenerative disease ( Wang et al, 2016 ) . Atp8a1, ATPase phospholipid transporting 8A1, may be implicated in neuroprotective effects caused by pumping phosphatidylserine across the plasma membrane ( Wang et al, 2023 ). In addition, the protein encoded by the Vsnl1 gene is a calcium sensor that is known to be increased in cerebrospinal fluid in Alzheimer’s patients and may be linked to disease progression ( Liao et al, 2022 ; Zetterberg, 2017 ).…”

Sex, Body Mass Index, and APOE4 Increase Plasma Phospholipid–Eicosapentaenoic Acid Response During an ω-3 Fatty Acid Supplementation: A Secondary Analysis

“…[ 48 ]. A recent study in 2023 found that phosphatidylserine (PS) EPA had neuroprotective effects on primary hippocampal neurons [ 49 ]. The authors of that study found that incubation of hippocampal nerves with PS-EPA increased p-CREB (cyclic adenosine monophosphate-dependent response element-binding protein) expression by 159% ( P < 0.05), whereas PS-DHA did not have a significant effect.…”

“…Interestingly, in this same study, synuclein expression increased to 130% after incubation with EPA-PS ( P < 0.05) but was not significantly affected after incubation with DHA-PS. Moreover, apoptosis Bcl-2 protein that acts as an inhibitor of the apoptotic pathway increased by 92% and 21% in the EPA-PS–treated and DHA-PS–treated neurons, respectively [ 49 ]. These findings emphasize the significant role of various PL-EPA species in preventing and mitigating neurodegeneration and suggest potential preventive measures for neurodegenerative diseases like AD.…”