Ethanolamine and vinyl-ether moieties in brain phospholipids modulate behavior in rats

Abstract Background Plasmalogens are brain-enriched phospholipids with a vinyl-ether bond at the sn-1 position between the glycerol backbone and alkyl chain. Previous studies have suggested that plasmalogens modulate locomotor activity, anxiety-like behavior, and cognitive functions, including learning and memory, in rodents; however, the specific moieties contributing to behavioral regulation are unknown. In this study, we examined behavioral modulation by specific phospholipid moieties by injecting rats with brain-permeable phospholipid liposomes prior to behavioral testing. Results To confirm that phospholipids in injected liposomes were incorporated into the brain, we first measured fluorescence intensity following intravenous injection of liposomes containing ATTO 740-labeled dioleoylphosphatidylethanolamine. We then compared the behavioral effects following injection of saline (control), egg phosphatidylcholine (PC) liposomes, or liposomes composed of egg PC and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (18:0–22:6 PE), 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0–22:6 PC), 1-(1Z-octadecenyl)-2-docosahexaenoyl-sn-glycero-3-phosphoethanolamine (18:0p-22:6 PE), or 1-(1Z-octadecenyl)-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0p-22:6 PC) into the tail vein of male rats. The time spent in the central region of the open field was significantly reduced by injection of 18:0–22:6 PE, which harbors an ester bond at sn-1, but not by 18:0p-22:6 PE, which harbors a vinyl-ether bond at sn-1, compared to saline-injected controls. Two-factor ANOVA also revealed a significant interaction effect between the hydrophilic head group (choline or ethanolamine) and the sn-1 position bond (ester or vinyl-ether) on discrimination ratio in the novel object recognition test, suggesting that substitution of an ester bond with a vinyl-ether bond at sn-1 in PE (18:0p-22:6 PE) but not in PC (18:0p-22:6 PC) can enhance recognition memory. Alternatively, there was no significant behavioral difference in the elevated plus maze or marble burying test. Conclusions We demonstrate that the hydrophilic moiety (head group) and sn-1 bond structure of brain plasmalogens can modulate cognitive function and locomotor activity in rodents.