Administration of Myo-inositol Plus Ethanolamine Elevates Phosphatidylethanolamine Plasmalogen in the Rat Cerebellum

Abstract

Plasmalogens are ether-linked phospholipids highly abundant in nervous tissue. Previously we demonstrated that acute administration of myo-inositol (myo-Ins) + [2-(13)C] ethanolamine ([2-(13)C]Etn) significantly elevated phosphatidylethanolamine plasmalogen (PlsEtn) in rat whole brain. Current experiments investigated the effects of acute myo-Ins+[2-(13)C]Etn administration on [PlsEtn] and the biosynthesis of new Etn lipids using NMR spectroscopy in rat cerebral cortex, hippocampus, brainstem, midbrain and cerebellum. Treated rats received a single dose of myo-Ins + [2-(13)C]Etn and controls received saline rather than myoIns. Data reveal that the cerebellum is the brain region most affected by treatment, which resulted in a 22% increase in [PlsEtn] and 89% increase in newly synthesized Etn lipids relative to controls (P < 0.05). Furthermore, the cerebellar PlsEtn/phosphatidylethanolamine ratio and molar percentage of PlsEtn were significantly elevated by 12% and 8%, respectively (P < 0.05). These data suggest that myo-Ins influences Etn lipid metabolism in brain, particularly in the cerebellum where there is a stimulation in the biosynthesis of new Etn lipids with a preference towards PlsEtn.

Extrinsic effectors regulating genes for plasmalogen biosynthetic enzymes in HepG2 cells

“…Monounsaturated long-chain fatty acids such as oleic acid (C18:1) and erucic acid (C22:1), myo-inositol, and Pl precursors, alkylglycerol and HG, have been reported to increase Pl levels in laboratory animals and humans [19][20][21][22][23]. However, they unexpectedly reduced the gene expression of Pl biosynthetic enzymes in HepG2 cells (Table 2).…”

“…Accordingly, we attempted to increase the levels of plasma Pls as a preventative strategy for diseases associated with oxidative stress and aging. This was achieved in laboratory animals as well as humans through administration of the Pl precursor alkylglycerol [19], myoinositol (MI) [20,21], monounsaturated long-chain fatty acids [22], and the hypolipidemic agent, statin [23]. However, their effects on the gene expression of Pl biosynthetic enzymes remain unknown.…”

Evidence that Plasmalogen is Protective Against Oxidative Stress in the Rat Brain

“…The effects of myo-Ins+Etn were further investigated in specific brain areas including brainstem, cerebral cortex, cerebellum, hippocampus and midbrain [13]. Our data revealed differential effects of this treatment protocol whereby the cerebellum was the region most affected by the administration of myo-Ins+Etn showing a significant increase in Etn lipid biosynthesis (89%), and elevations in PlsEtn (22%) and myo-Ins concentrations (23%) [13].…”

“…Our data revealed differential effects of this treatment protocol whereby the cerebellum was the region most affected by the administration of myo-Ins+Etn showing a significant increase in Etn lipid biosynthesis (89%), and elevations in PlsEtn (22%) and myo-Ins concentrations (23%) [13]. In the present investigation, we used this same myo-Ins+Etn protocol to test the therapeutic effects of elevated PlsEtn within the rat brain.…”

“…Recently, our laboratory further investigated this phenomenon using several protocols involving chronic and acute administration of myo-Ins±ethanol-amine (Etn) in the rat brain [12,13]. The addition of Etn containing 13 C isotope enrichment enabled us to monitor the biosynthesis of Etn lipids in the brain by NMR spectroscopy.…”