Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro

The brain is more highly enriched than most other tissues in long-chain polyunsaturated fatty acids (PUFA), particularly docosahexaenoic acid (DHA). In vitro studies of PUFA synthesis and release utilizing cell cultures of astrocytes, neurons, and cerebral microvascular endothelium have contributed significantly to our understanding of mechanisms potentially involved in the accretion of PUFA in brain. Both cerebral endothelium and astrocytes avidly elongate and desaturate precursors of the long-chain PUFAs when grown individually or in various co-culture combinations. The products, such as arachidonic acid (AA) and DHA, are released from the cells. In contrast, neurons appear unable to carry out fatty acid desaturation and thus are dependent upon preformed long-chain PUFA. Indeed, neurons co-cultured with astrocytes accumlate docosahexaenoate synthesized by the glial cells. Cerebral endothelial cultures are additionally capable of enriching the basolateral compartment (analogous to the brain extracellular space) with n-3 PUFA when grown in a membrane/chamber apparatus. The enrichment of this compartment with DHA is increased when cerebral endothelium is co-cultured with astrocytes. These data suggest that endothelial cells and astrocytes cooperate in the local synthesis and release of PUFA, collectively maintaining a brain environment enriched in long-chain PUFA.