Efficient Docosahexaenoic Acid Uptake by the Brain from a Structured Phospholipid

Mayssa Hachem, Alain Géloën, Amanda Lo Van, Baptiste Foumaux, Laurence Fenart, Fabien Gosselet, Pedro Da Silva, Gildas Breton, Michel Lagarde, Madeleine Picq, Nathalie Bernoud-Hubac

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

Docosahexaenoic acid (DHA) is the main essential omega-3 fatty acid in brain tissues required for normal brain development and function. An alteration of brain DHA in neurodegenerative diseases such as Alzheimer’s and Parkinson’s is observed. Targeted intake of DHA to the brain could compensate for these deficiencies. Blood DHA is transported across the blood–brain barrier more efficiently when esterified at the sn-2 position of lyso-phosphatidylcholine. We used a structured phosphatidylcholine to mimic 2-docosahexaenoyl-lysoPC (lysoPC-DHA), named AceDoPC (1-acetyl,2-docosahexaenoyl-glycerophosphocholine), that may be considered as a stabilized form of the physiological lysoPC-DHA and that is neuroprotective in experimental ischemic stroke. The aim of the present study was to investigate whether AceDoPC is a relevant delivery form of DHA to the brain in comparison with other forms of the fatty acid. By combining in vitro and in vivo experiments, our findings report for the first time that AceDoPC is a privileged and specific carrier of DHA to the brain, when compared with DHA-containing PC and non-esterified DHA. We also show that AceDoPC was hydrolyzed, in part, into lysoPC-DHA. Ex vivo autoradiography of rat brain reveals that DHA from AceDoPC was localized in specific brain regions playing key roles in memory, thoughts, and cognitive functions. Finally, using molecular modeling approaches, we demonstrate that electrostatic and lipophilic potentials are distributed very similarly at the surfaces of AceDoPC and lysoPC-DHA. Our findings identify AceDoPC as an efficient way to specifically target DHA to the brain, which would allow potential preventive and therapeutic approaches for neurological diseases.

Original languageBritish English
Pages (from-to)3205-3215
Number of pages11
JournalMolecular Neurobiology
Volume53
Issue number5
DOIs
StatePublished - 1 Jul 2016

Keywords

  • Blood–brain barrier
  • Brain
  • Docosahexaenoic acid
  • Lyso-phosphatidylcholine
  • Transport

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