Oral administration of ethanolamine glycerophospholipid containing a high level of plasmalogen improves memory impairment in amyloid β-infused rats

Image of sea squirts.

Yamashita S, Hashimoto M, Haque AM, Nakagawa K, Kinoshita M, Shido O, and Miyazawa T. (2017) Oral administration of ethanolamine glycerophospholipid containing a high level of plasmalogen improves memory impairment in amyloid β-infused rats. Lipids

Plasmalogens are a unique class of lipids that contain a vinyl-ether bond, giving this group of lipids distinctive characteristics. This bond provides a more compact structure to plasmalogens establishing their importance in cellular membrane organization and fluidity, as well as vesicular fusion. Plasmalogens also have antioxidant properties because the vinyl bond is able to scavenge two radial oxygen species. Although found ubiquitously through a human body, plasmalogens make up the greatest phospholipid component in the brain. Reduced levels of plasmalogens have been associated with Alzheimer’s disease (AD), a progressive neurological disorder characterized by memory loss and declining cognitive abilities. Common to AD pathology is the presence of beta-amyloid (Aβ), a toxic protein that can aggregate and is thought to cause some of the atrophy seen in AD post-mortem brains and exacerbate oxidative stress present. Yamashita et al used an AD rat model through Aβ-infusion to determine if plasmalogen supplementation could improve memory and plasmalogen levels.

To determine the role of plasmalogens in learning, plasmalogens were isolated from two sources to provide a low (egg yolk) and a high (ascidian viscera; sea squirt) treatment. To test the effect of plasmalogen treatment on learning ability, the radial maze test was used to examine the reference memory errors (RMEs; long-term memory) and working memory errors (WMEs; short-term memory) from rats in the treatment groups. After four weeks of being fed the sea squirt-supplemented food, both the RME and WME were lower than the group fed plasmalogens from the egg yolk and the control group, fed a regular diet. Notably, the WME score for the rats fed sea squirt plasmalogens was almost half of that seen in the other two groups at ~1.3 compared to ~2.6. Interestingly, the egg yolk group did not improve WMEs or RMEs.

It was also investigated whether any changes in plasmalogen levels could be found within the plasma, liver, and brain of the rats. After the rats were treated for six weeks, docosahexaenoic acid (DHA) was increased in the serum of both the sea squirt and the egg yolk treatment groups. The sea squirt group also showed greater levels of plasmalogens at ~105 nmol/mL compared to the control group at ~17 nmol/mL. Specifically, 18:0/22:6 showed an increase from 3.7 to 26.5 nmol/mL plasma and 18:0/20:4 increased from 6.7 nmol/mL to 29.9 nmol/mL. The liver also showed higher 18:2n-6 (32.3 nmol/mL) and DHA (0.52 nmol/mL) levels in the sea squirt-treated group while the control group had levels of 22.7 nmol/mL and 0.29 nmol/mL, respectively. When looking at specific species of plasmalogens, 18:0/22:6 and 18:0/20:5 showed the greatest increases from control at 209 and ~20 nmol/mg protein to 720 and 155 nmol/mg protein, respectively, in the sea squirt treatment group. Both the cerebral cortex and the hippocampus did not show any differences between the three groups.

Yamashita et al were interested in whether plasmalogen supplementation using lipids from either sea squirts or egg yolk could improve working memory or reference memory in Aβ-infused rats and whether the treatments would alter plasmalogen levels in tissues and plasma. The sea squirt treatment proved more successful across all measurements compared to the egg yolk. Although both phospholipid treatments were administered at 260 μmol/kg, equivalent to almost 200 mg/kg, the sea squirt treatment had a much greater level of plasmalogens detected at 80% of the phospholipid treatment, while the egg yolk only contained 4% plasmalogens. As the yolk treatment was actually much lower, it is unsurprising that the sea squirt showed a benefit to rat memory, while the egg yolk did not. These findings give support for the role of plasmalogens in memory, compared to phospholipids. If memory improvement resulted from overall phospholipid increases, then it would have been expected to see similar improvements from both the sea squirt and egg yolk treatments, as they both deliver around 200mg/kg of phospholipids. For diseases such as AD, the greatest benefit would come from being able to augment brain levels. Although this was not seen in this study, it is promising that there were memory improvements in the highest treatment group. Based on the results found by Yamashita et al, further work looking at higher doses than used in this study or more specificity of the plasmalogen species within the treatment could increase the benefits shown.