Moore S A, Yoder E, Murphy S, Dutton G R, Spector A A
Department of Pathology, University of Iowa, Iowa City.
J Neurochem. 1991 Feb;56(2):518-24. doi: 10.1111/j.1471-4159.1991.tb08180.x.
Elongated, highly polyunsaturated derivatives of linoleic acid (18:2 omega-6) and linolenic acid (18:3 omega-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] 18:2 omega-6, [1-14C]20:4 omega-6, [1-14C]18:3 omega-3, or [1-14C]20:5 omega-3 and their elongation/desaturation products determined. Neuronal cultures were routinely incapable of producing significant amounts of delta 4-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 18:2 omega-6 was 20:4 omega-6, whereas the primary products from 18:3 omega-3 were 20:5 omega-3, 22:5 omega-3, and 22:6 omega-3. The majority of the long-chain fatty acids formed by astrocyte cultures, particularly 20:4 omega-6 and 22:6 omega-3, was released into the extracellular fluid. Although incapable of producing 20:4 omega-6 and 22:6 omega-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 omega-6 and omega-3 essential fatty acid precursors to 20:4 omega-6 and 22:6 omega-3, then releasing the long-chain polyunsaturated fatty acids for uptake by neurons.
亚油酸（18:2 ω-6）和亚麻酸（18:3 ω-3）的延长型、高度多不饱和衍生物在大脑中蓄积，但其合成部位尚未完全明确。为研究神经元自身是否能够进行必需脂肪酸的延长和去饱和，还是依赖于其他脑细胞的支持，将大鼠神经元和星形胶质细胞的原代培养物与[1-14C] 18:2 ω-6、[1-14C]20:4 ω-6、[1-14C]18:3 ω-3或[1-14C]20:5 ω-3一起孵育，并测定其延长/去饱和产物。神经元培养物通常无法产生大量的δ4-去饱和酶产物。它们在该途径的每个步骤中对脂肪酸的去饱和能力都很差，主要产生18碳和20碳前体的延长产物。相比之下，星形胶质细胞能够积极地延长和去饱和18碳和20碳前体。18:2 ω-6的主要代谢产物是20:4 ω-6，而18:3 ω-3的主要产物是20:5 ω-3、22:5 ω-3和22:6 ω-3。星形胶质细胞培养物形成的大多数长链脂肪酸，特别是20:4 ω-6和22:6 ω-3，会释放到细胞外液中。虽然神经元培养物无法从前体脂肪酸产生20:4 ω-6和22:6 ω-3，但它们很容易从培养基中摄取这些脂肪酸。这些发现表明，星形胶质细胞通过将ω-6和ω-3必需脂肪酸前体延长和去饱和为20:4 ω-6和22:6 ω-3，然后释放长链多不饱和脂肪酸供神经元摄取，在大脑中发挥重要的支持作用。
