Astrocytes, Not Neurons, Produce Docosahexaenoic Acid (22:6ω‐3) and Arachidonic Acid (20:4ω‐6)

Abstract: Elongated, highly polyunsaturated derivatives of linoleic acid (18:2ω‐6) and linolenic acid (18:3ω‐3) accumulate in brain, but their sites of synthesis are not fully characterized. To investigate whether neurons themselves are capable of essential fatty acid elongation and desaturation or are dependent upon the support of other brain cells, primary cultures of rat neurons and astrocytes were incubated with [1‐14C]18:2ω‐6, [1‐14C]20:4ω‐6, [1‐14C]18:3ω‐3, or [1‐14C]20:5ω‐3 and their elongation/desaturation products determined. Neuronal cultures were routinely incapable of producing significant amounts of Δ4‐desaturase products. They desaturated fatty acids very poorly at every step of the pathway, producing primarily elongation products of the 18‐ and 20‐carbon precursors. In contrast, astrocytes actively elongated and desaturated the 18‐ and 20‐carbon precursors. The major metabolite of 18:2ω‐6 was 20:4ω‐6, whereas the primary products from 18:3ω‐3 were 20:5ω‐3, 22:5ω‐3, and 22:6ω‐3. The majority of the long‐chain fatty acids formed by astrocyte cultures, particularly 20:4ω‐6 and 22:6ω‐3, was released into the extracellular fluid. Although incapable of producing 20:4ω‐6 and 22:6ω‐3 from precursor fatty acids, neuronal cultures readily took up these fatty acids from the medium. These findings suggest that astrocytes play an important supportive role in the brain by elongating and desaturating ω‐6 and ω‐3 essential fatty acid precursors to 20:4ω‐6 and 22:6ω‐3, then releasing the long‐chain polyunsaturated fatty acids for uptake by neurons.