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Researchers at UCLA School of Medicine David Geffen, UCLA Howard Hughes Medical Institute, and the National Institutes of Health have developed a zebrafish model that provides new insight into how the brain acquires essential omega-3 fatty acids, including docosahexaenoic acid (DHA). ) and linolenic acid (ALA). Their findings, published in Nature CommunicationsIt has the potential to improve understanding of lipid transport across the blood-brain barrier and perturbations in this process that can lead to birth defects or neurological conditions. The model may also enable researchers to design drug molecules that are able to get directly into the brain.
Omega-3 fatty acids are essential because the body cannot make them and must be obtained through foods such as fish, nuts and seeds. DHA levels are particularly high in the brain and are important for a healthy nervous system. Babies get DHA from breast milk or formula, and deficiencies in this fatty acid have been linked to problems with learning and memory. To get to the brain, omega-3 fatty acids must pass through the blood-brain barrier via the lipid transporter Mfsd2a, which is essential for normal brain development. Despite its importance, scientists didn’t know exactly how Mfsd2a transports DHA and other omega-3 fatty acids.
In the study, the research team provided images of the structure of the Mfsd2a zebrafish, which is similar to its human counterpart. The snapshots are the first to accurately detail how fatty acids move across a cell membrane. The study team also identified three compartments in Mfsd2a that indicate distinct steps required to move and flip fatty acids across the transporter, as opposed to movement through a linear tunnel or along the surface of a protein complex. The findings provide key information about how Mfsd2a transports omega-3 fatty acids into the brain and may enable researchers to improve drug delivery via this route. The study also provides key knowledge about how other members of this transporter family, called the major facilitator family (MFS), regulate important cellular functions.
The study was led by Tamir Gonen, PhD, of UCLA and Doreen Mathis, PhD, of the National Institutes of Health. Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Additional funding for the study was provided by the National Institute of General Medical Sciences of the National Institutes of Health (NIGMS) and the Howard Hughes Medical Institute.
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