Findings may aid the design of models and targeted drug delivery into the brain and central nervous system.
Intelligence, brain – artistic concept. Image credit: geralt via Pixabay, free license
Researchers at the National Institutes of Health and colleagues 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 Communications, can potentially improve understanding and modeling of lipid transport across the blood-brain barrier and disruptions in this process that can lead to birth defects or neurological conditions.
The model may also enable researchers to design drug molecules that can directly reach the brain.
Docosahexaenoic acid (DHA) is an essential omega-3 fatty acid important for a healthy nervous system. This model shows how DHA and other omega-3 fatty acids cross the blood-brain barrier through the lipid transporter Mfsd2a. Image credit: Ethan Tyler, NIH Medical Arts
Omega-3 fatty acids are considered essential because the body cannot make them and must obtain them through foods, such as fish, nuts and seeds.
DHA levels are especially high in the brain and important for a healthy nervous system. Infants obtain DHA from breastmilk or formula, and deficiencies of 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, essential for normal brain development. Despite its importance, scientists did not know precisely how Mfsd2a transports DHA and other omega-3 fatty acids.
In the study, the research team provides images of the structure of zebrafish Mfsd2a, which is similar to its human counterpart. The snapshots are the first to detail precisely how fatty acids move across the cell membrane.
The study team also identified three compartments in Mfsd2a that suggest distinct steps required to move and flip fatty acids through the transporter, as opposed to movement through a linear tunnel or along the surface of the protein complex.
The findings provide key information on how Mfsd2a transports omega-3 fatty acids into the brain and may enable researchers to optimize drug delivery via this route. The study also provides foundational knowledge on how other members of this transporter family, called the major facilitator superfamily (MFS), regulate important cellular functions.
Source: NIH