Department of Physiology, Faculty of Medicine, Complutense University, 28040, Madrid, Spain.
Natac Pharma S.L., 28923, Alcorcón, Madrid, Spain.
Neuromolecular Med. 2018 Sep;20(3):328-342. doi: 10.1007/s12017-018-8496-8. Epub 2018 May 30.
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 (ω-3) long chain polyunsaturated fatty acid of neuronal membranes involved in normal growth, development, and function. DHA has been proposed to reduce deleterious effects in neurodegenerative processes. Even though, some inconsistencies in findings from clinical and pre-clinical studies with DHA could be attributed to the presence of phytanic acid (PhA) in standard DHA treatments. Thus, the aim of our study was to analyze and compare the effects of a low PhA-concentrated DHA with a standard PhA-concentrated DHA under different neurotoxic conditions in BV-2 activated microglial cells. To this end, mouse microglial BV-2 cells were stimulated with either lipopolysaccharide (LPS) or hydrogen peroxide (HO) and co-incubated with DHA 50 ppm of PhA (DHA (PhA:50)) or DHA 500 ppm of PhA (DHA (PhA:500)). Cell viability, superoxide anion (O) production, Interleukin 6 (L-6), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), glutathione peroxidase (GtPx), glutathione reductase (GtRd), Caspase-3, and the brain-derived neurotrophic factor (BDNF) protein expression were explored. Low PhA-concentrated DHA protected against LPS or HO-induced cell viability reduction in BV-2 activated cells and O production reduction compared to DHA (PhA:500). Low PhA-concentrated DHA also decreased COX-2, IL-6, iNOS, GtPx, GtRd, and SOD-1 protein expression when compared to DHA (PhA:500). Furthermore, low PhA-concentrated DHA increased BDNF protein expression in comparison to DHA (PhA:500). The study provides data supporting the beneficial effect of low PhA-concentrated DHA in neurotoxic injury when compared to a standard PhA-concentrated DHA in activated microglia.
二十二碳六烯酸(DHA,22:6n-3)是神经元膜中必需的ω-3(ω-3)长链多不饱和脂肪酸,参与正常的生长、发育和功能。DHA 被认为可以减轻神经退行性过程中的有害影响。然而,DHA 的临床和临床前研究结果存在一些不一致之处,这可能归因于标准 DHA 治疗中存在植烷酸(PhA)。因此,我们的研究目的是分析和比较在 LPS 或 H2O2 刺激的 BV-2 激活小胶质细胞中,低 PhA 浓缩 DHA 与标准 PhA 浓缩 DHA 对不同神经毒性条件的影响。为此,用 LPS 或 H2O2 刺激小鼠小胶质细胞 BV-2,并与 50ppm PhA 的 DHA(DHA(PhA:50))或 500ppm PhA 的 DHA(DHA(PhA:500))共孵育。检测细胞活力、超氧阴离子(O)生成、白细胞介素 6(L-6)、环氧化酶-2(COX-2)、诱导型一氧化氮合酶(iNOS)、谷胱甘肽过氧化物酶(GtPx)、谷胱甘肽还原酶(GtRd)、Caspase-3 和脑源性神经营养因子(BDNF)蛋白表达。与 DHA(PhA:500)相比,低 PhA 浓缩 DHA 可防止 LPS 或 H2O2 诱导的 BV-2 激活细胞活力降低和 O 生成减少。与 DHA(PhA:500)相比,低 PhA 浓缩 DHA 还降低了 COX-2、IL-6、iNOS、GtPx、GtRd 和 SOD-1 蛋白表达。此外,与 DHA(PhA:500)相比,低 PhA 浓缩 DHA 增加了 BDNF 蛋白表达。该研究提供的数据支持了低 PhA 浓缩 DHA 在激活小胶质细胞中神经毒性损伤时的有益作用,与标准 PhA 浓缩 DHA 相比。