Structure-specific, accurate quantitation of plasmalogen glycerophosphoethanolamine

Morel Y, Hegdekar N, Sarkar C, Lipinski MM, Kane MA, Jones JW. (2021) Structure-specific, accurate quantitation of plasmalogen glycerophosphoethanolamine. Analytica Chimica Acta, 1186

Glycerophosphoethanolamines (PE) are the second most prevalent glycerophospholipids in cell membranes. One class of PE are plasmalogens, lipids that contain a vinyl-ether bond at sn-1. This bond causes plasmalogens to have a more compact structure, giving plasmalogens roles in membrane structure, organization, and fluidity as well as vesicular fusion, cholesterol transport, and antioxidative properties. A reduction in plasmalogens has been associated with a wide range of disorders including Zellweger’s syndrome, rhizomelic chondrodysplasia punctata, multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease which is unsurprising considering their important roles in cells. Previous work by Morel et al had demonstrated that lysosomes from brains of mice following traumatic brain injury (TBI) have altered plasmalogen levels. To investigate neurodegeneration further, plasmalogen concentration in plasma was studied in a mouse model of TBI.

TBI was induced through controlled cortical impact (CCI) in C57BL/6J mice, then their blood was collected at 1, 3, 7, 14, and 28 days after TBI to analyze their plasmalogen levels using liquid chromatography tandem mass spectrometry (LC-MS). After developing and validating a new method to quantify plasmalogens in plasma, 112 different lipid classes were measured, with 54 types found. Morel et al observed that plasmalogens with a saturated sn-1 chain (in addition to the vinyl-ether bond) were significantly elevated 24 hours after TBI. As well, plasmalogens with sn-2 acyl chains of 18:2, 20:4, and 22:6 were the most abundant and, of all the plasmalogen species tested, 18:1, 18:2, 18:3, 20:4, and 22:6 demonstrated the greatest increase after the TBI procedure. Morel et al also noted that of all PEs, plasmalogens were most significantly changed from the sham group to day 1 after TBI with an increase seen after injury. Following this increase, almost all plasmalogen species were lower than the sham group concentrations by 7 days post injury and showed a return to sham levels by 28 days. This is consistent with other literature following brain injury. It is interesting that the plasmalogen species returned to sham concentrations after 28 days because this would suggest that the circulating plasmalogens could equilibrate and return to normal levels following brain injury.

Oxidative damage during disease can produce degradation products including lysophospholipids (LPE), therefore, Morel et al also measured LPEs in the plasma from these animals. Similar to the plasmalogens, lysophosphoethanolamines (LPE-P) increased 1 day after TBI compared to the sham group, but outside of this finding there was no trending temporal change in LPE concentrations as they returned to roughly sham levels by day 3 with a minor decrease on day 28. However, some LPE species actually decreased compared to the sham group 1 day post TBI before returning to levels near the sham concentrations.

Morel et al were interested in looking at changes in plasmalogens and other phospholipids following neurodegeneration following brain injury using a TBI mouse model. This work demonstrated that plasmalogens can be an indicator for systemic response immediately following brain injury. As well, the fact that examining phospholipids containing the vinyl-ether at sn-1 and those with saturated sn-2 chains both showed similar increases over the first 24 hours following brain injury would indicate that phosphoethanolamine structure was differentially affected in this response. However, it is mentioned that enzymatic activity should not be directly inferred on LPE presence when phospholipidase activity is not also measured, but in a well-characterized model it would provide support and a further explanation behind the levels of other phospholipid components. It is important that brain injuries are diagnosed quickly, therefore if plasmalogens and their degradation products can be quantified from a plasma sample, this would be a fast initial confirmation. More work to determine a firm baseline for standard plasmalogen levels in humans and the changes that occur following brain injury could further progress the development of using plasmalogen and other phospholipid levels as a marker of TBI.