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.