Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: An in situ cerebral perfusion study

Melissa Ouellet, Vincent Emond, Chuck T. Chen, Carl Julien, Fanchon Bourasset, Salvatore - Oddo, Frank LaFerla, Richard P. Bazinet, Frédéric Calon

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids are n-3 polyunsaturated fatty acids with a therapeutic potential for CNS diseases. Here, using an in situ brain perfusion technique in mice, we show that [14C]-DHA and [14C]-EPA readily cross the mouse blood-brain barrier (BBB) with brain transport coefficients (Clup) of 48 ± 3 μl g-1 s-1 and 52 ± 4 μl g-1 s-1, respectively. Mechanical capillary depletion of brain homogenates showed that less than 10% of [14C]-DHA or [14C]-EPA remained in endothelial cells of the brain vasculature, demonstrating that both molecules fully crossed the BBB. Addition of bovine serum albumin decreased the Clup of [14C]-DHA to 0.6 ± 0.3 μl g-1 s-1, indicating that binding to albumin reduced importantly, but not totally, the passage of DHA through the BBB. The Clup of [14C]-DHA or [14C]-EPA was not saturable at concentration up to 100 μM, suggesting that these compounds crossed the BBB by simple diffusion. However, long-term high-DHA dietary consumption reduced the Clup of [14C]-DHA to 33 ± 6 μl g-1 s-1 (-20%, p < 0.01). These results confirm that the brain uptake of DHA or EPA perfused with a physiological buffer is comparable to highly diffusible drugs like diazepam, and can be modulated by albumin binding and chronic dietary DHA intake.

Original languageEnglish (US)
Pages (from-to)476-482
Number of pages7
JournalNeurochemistry International
Volume55
Issue number7
DOIs
StatePublished - Dec 2009
Externally publishedYes

Fingerprint

Eicosapentaenoic Acid
Docosahexaenoic Acids
Blood-Brain Barrier
Perfusion
Brain
Albumins
Central Nervous System Diseases
Omega-3 Fatty Acids
Diazepam
Bovine Serum Albumin
Buffers
Endothelial Cells
Pharmaceutical Preparations

Keywords

  • Blood-brain barrier
  • Docosahexaenoic acid
  • Eicosapentaenoic acid
  • In situ brain perfusion

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier : An in situ cerebral perfusion study. / Ouellet, Melissa; Emond, Vincent; Chen, Chuck T.; Julien, Carl; Bourasset, Fanchon; Oddo, Salvatore -; LaFerla, Frank; Bazinet, Richard P.; Calon, Frédéric.

In: Neurochemistry International, Vol. 55, No. 7, 12.2009, p. 476-482.

Research output: Contribution to journalArticle

Ouellet, Melissa ; Emond, Vincent ; Chen, Chuck T. ; Julien, Carl ; Bourasset, Fanchon ; Oddo, Salvatore - ; LaFerla, Frank ; Bazinet, Richard P. ; Calon, Frédéric. / Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier : An in situ cerebral perfusion study. In: Neurochemistry International. 2009 ; Vol. 55, No. 7. pp. 476-482.
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