The barrier weakens with age and in APOE4 carriers; DHA in phospholipid form crosses it via the Mfsd2a transporter and protects it.
View the study (preclinical) →Toll-like receptors 4 on its endothelial cells detect LPS and trigger inflammation that increases permeability: a gut-brain vicious circle.
Altered barrier permeability contributes to the neuroinflammation that accompanies dopaminergic loss.
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The blood-brain barrier is one of the most sophisticated structures of the human body and, at the same time, one of the most vulnerable to the accumulated insults of aging, obesity, chronic inflammation, and exposure to environmental toxins; its function is to protect the brain from the bloodstream, letting through the nutrients and chemical signals that the nervous system needs while blocking pathogens, toxins, and immune cells that would cause damage if they accessed neural tissue freely; when this barrier fails, the consequences are far-reaching and contribute to the pathogenesis of conditions as diverse as Alzheimer's, Parkinson's, depression, and multiple sclerosis.
The barrier is formed by specialized endothelial cells that line the brain capillaries and that differ from the endothelial cells in the rest of the body by the presence of tight junctions that limit the paracellular passage of molecules, and by the almost total absence of vesicular transcytosis, which would allow molecules to cross through the interior of the cells; this difference is fundamental: whereas capillaries in the lung, for example, make extensive use of transcytosis to exchange molecules with the environment, brain capillaries actively suppress it to maintain the integrity of the barrier.
Docosahexaenoic acid or DHA, the long-chain omega-3 fatty acid of marine origin, plays a critical role in maintaining the integrity of the blood-brain barrier through a fascinating molecular mechanism: brain endothelial cells express the Mfsd2a transporter, which is the only route by which DHA in the form of phospholipids can enter the brain, and studies in mice with mutations that block this transporter have shown that the absence of Mfsd2a drastically reduces barrier integrity, increases the formation of caveolae, which are the vesicular structures that the brain normally suppresses to control what enters, and progressively impairs neuronal function.
The reason DHA protects the barrier lies in membrane chemistry: phospholipids containing DHA form extremely fluid and disordered structures that are incompatible with the formation of "lipid rafts," which are the ordered areas of the membrane where caveolae preferentially form; that is, the more DHA there is in the membranes of brain endothelial cells, the less transcytosis occurs and the more intact the barrier remains against toxins, pathogens, and abnormal proteins such as amyloid.
Intestinal permeability and blood-brain barrier permeability are connected bidirectionally through the gut-brain axis: when the intestinal barrier weakens, bacterial endotoxins, particularly lipopolysaccharide or LPS from gram-negative bacteria, enter the bloodstream, activate toll-like receptor 4 on brain endothelial cells, and induce inflammation that increases the permeability of the blood-brain barrier; this vicious circle of intestinal permeability that promotes neuroinflammation, which in turn impairs the gut-brain axis, is one of the mechanisms by which gut dysbiosis has been associated with neurodegenerative diseases, mood disorders, and accelerated cognitive decline.
Information, not medical advice. Scientific evidence reflects the quality of the studies.