Investigation of Lysophospholipids-DHA transport across an in vitro human model of blood brain barrier

Abstract

Several studies emphasized on the preventive and therapeutic potential of Docosahexaenoic Acid (DHA, 22:6n-3) supplementation in chronic and age-related disorders including neurodegenerative diseases. Researchers principally studied the cerebral accretion of Lysophosphatidylcholine (LysoPC-DHA), the furthermost vital Lysophospholipid-DHA (LysoPL-DHA) in blood plasma. Nevertheless, the cerebral bioavailability of other LysoPL-DHA forms including Lysophosphatidylethanolamine (LysoPE-DHA), and Lysophosphatidylserine (LysoPS-DHA) were not extensively examined even though their vital biological functions in the brain. Hence, the aim of the present study was to evaluate the toxicity and transport of DHA in comparison to several LysoPL-DHA including LysoPC-DHA, LysoPE-DHA and LysoPS-DHA across a human model of blood-brain barrier (BBB). The human brain-like endothelial cells (hBLECs) monolayer tightness was evaluated by the parallel assessment of the permeability of fluorescent marker Lucifer yellow (LY) and revealed the absence of toxicity of non-esterified DHA and all LysoPL-DHA towards hBLECs. LysoPC-DHA, LysoPE-DHA and LysoPS-DHA displayed a higher recovery in the abluminal medium in comparison to non-esterified DHA at 30, 60 and 120 min post-incubation. Among all, LysoPS-DHA revealed the highest apparent coefficient permeability (Papp) 85.87 ± 4.24 x 10−6 cm s−1 and was significantly different than DHA, LysoPC-DHA and LysoPE-DHA. More interestingly, when studying the time course of Papp of DHA, LysoPC-DHA and LysoPE-DHA, at different post-incubation time, this permeability decreases with time especially for LysoPC-DHA and LysoPE-DHA, not for DHA. Furthermore, LysoPS-DHA exhibited the highest intracellular accumulation (10.39 ± 0.49 %) in hBLECs in comparison to all other tested lipids. Finally, differences in 3D structures and molecular electrostatic potential maps calculation of LysoPL-DHA could explain the dissimilar cerebral uptake of LysoPL-DHA. Altogether, our findings raise the novel hypothesis that LysoPS-DHA may represent a preferred physiological carrier of DHA to the brain.