Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California, Davis, CA, USA; Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA.
Neurochem Int. 2023 Mar;164:105506. doi: 10.1016/j.neuint.2023.105506. Epub 2023 Feb 8.
Linoleic acid (LA, 18:2n-6) is an essential nutrient for optimal infant growth and brain development. The effects of LA in the brain are thought to be mediated by oxygenated metabolites of LA known as oxidized LA metabolites (OXLAMs), but evidence is lacking to directly support this hypothesis. This study investigated whether OXLAMs modulate key neurodevelopmental processes including axon outgrowth, dendritic arborization, cell viability and synaptic connectivity. Primary cortical neuron-glia co-cultures from postnatal day 0-1 male and female rats were exposed for 48h to the following OXLAMs: 1) 13-hydroxyoctadecadienoic acid (13-HODE); 2) 9-hydroxyoctadecadienoic acid (9-HODE); 3) 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME); 4) 12(13)-epoxyoctadecenoic acid (12(13)-EpOME); 5) 9,10,13-trihydroxyoctadecenoic acid (9,10,13-TriHOME); 6) 9-oxo-octadecadienoic acid (9-OxoODE); and 7) 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME). Axonal outgrowth, evaluated by Tau-1 immunostaining, was increased by 9-HODE, but decreased by 12,13-DiHOME in male but not female neurons. Dendrite arborization, evaluated by MAP2B-eGFP expression, was affected by 9-HODE, 9-OxoODE, and 12(13)-EpOME in male neurons and, by 12(13)-EpOME in female neurons. Neither cell viability nor synaptic connectivity were significantly altered by OXLAMs. Overall, this study shows select OXLAMs modulate neuron morphology in a sex-dependent manner, with male neurons being more susceptible.
亚油酸（LA，18:2n-6）是婴儿最佳生长和大脑发育所必需的营养物质。据认为，LA 在大脑中的作用是通过被称为氧化 LA 代谢物（OXLAMs）的 LA 含氧代谢物介导的，但缺乏直接支持这一假设的证据。本研究旨在探讨 OXLAMs 是否调节关键的神经发育过程，包括轴突生长、树突分支、细胞活力和突触连接。从雄性和雌性大鼠出生后第 0-1 天的皮质神经元-神经胶质共培养物中，将以下 OXLAMs 暴露 48 小时：1）13-羟基十八碳二烯酸（13-HODE）；2）9-羟基十八碳二烯酸（9-HODE）；3）9,10-二羟基十八碳烯酸（9,10-DiHOME）；4）12（13）-环氧十八碳烯酸（12（13）-EpOME）；5）9,10,13-三羟基十八碳烯酸（9,10,13-TriHOME）；6）9-氧代十八碳二烯酸（9-OxoODE）；和 7）12,13-二羟基十八碳烯酸（12,13-DiHOME）。通过 Tau-1 免疫染色评估的轴突生长，雄性神经元中 9-HODE 增加，但 12,13-DiHOME 减少，而雌性神经元中则没有。通过 MAP2B-eGFP 表达评估的树突分支，雄性神经元中 9-HODE、9-OxoODE 和 12（13）-EpOME 以及雌性神经元中 12（13）-EpOME 受到影响。OXLAMs 均未显著改变细胞活力或突触连接。总的来说，本研究表明，一些 OXLAMs 以性别依赖的方式调节神经元形态，雄性神经元更为敏感。
