New information on the importance of DHA in brain development
The brain is one of the most lipid-rich organs in the body. Docosahexaenoic acid (DHA) is found in large amounts in brain phospholipids, particularly phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine, and constitutes around 15% of the total fatty acid composition of the prefrontal cortex. At the end of the second trimester of human gestation, brain concentrations of DHA rise rapidly, coinciding with the development of the blood brain barrier. The accumulation of DHA in the brain continues up to approximately two years of age. Prenatal brain development is a complex process that involves the coordinated establishment of hundreds of specialised types of cells, and the creation of synaptic connectivity and the blood brain barrier. Postnatal brain growth involves the proliferation of astrocytes and oligodendrocytes, the myelinisation of axons and the expansion of neuronal dendrites. DHA is crucial in these states, but cannot be efficiently synthesised de novo in the brain; it has to be transported by crossing the blood brain barrier.
Crucial to the prenatal and postnatal stages of brain development are the biosynthesis of massive amounts of membrane phospholipids, which were thought to come exclusively from de novo synthesis in brain cells, and the obtaining of essential fatty acids from the periphery. It is now known that de novo synthesis is mediated by sterol regulatory-element binding protein (SREBP) transcription factors, while obtaining essential fatty acids is mediated by the major facilitator superfamily domain containing 2A (MFSD2A), which is expressed in the endothelium of the brain blood vessels and other brain cells.
Recently, a group of researcher in Singapore used a mouse model to determine that MFSD2A is required in the blood brain barrier for brain development and DHA accretion after birth (and that deficiencies are related to abnormalities such as microcephaly). They also determined that one of the main functions of DHA in the brain is to negatively regulate SREBP activation, which has profound effects on the phospholipid composition of the membrane. In DHA-deficient brains, the SREBP-1 and SREBP-2 pathways are much increased, but treatment of neural stem cells with LPC-DHA (lisophosphatidylcholine (LPC)-DHA, a natural form of DHA synthesised in the liver) produced MFSD2A-dependent down-regulation of their activation. This is the main form of DHA that can reach the brain, with the help of the specific transporter (MFSD2A), as other forms are unable to cross the blood brain barrier.
Two events have to occur for DHA to reach the brain in large enough quantities in these crucial period of brain development: the presence of MFSD2A transporters and the abundance of LPC-DHA. Dietary DHA does not reach the brain (it does not cross the blood brain barrier) unless the liver has converted it into LPC-DHA.
These findings provide more knowledge on the functions of DHA in the developing brain.