Oye Mintsa Mi-Mba Méryl-Farelle, Lebbadi Meryem, Alata Waël, Julien Carl, Emond Vincent, Tremblay Cyntia, Fortin Samuel, Barrow Colin J, Bilodeau Jean-François, Calon Frédéric
Faculty of Pharmacy, Laval University, Quebec, QC, Canada; Centre Hospitalier de l'Université Laval (CHUL) Research Center, Quebec, QC, Canada.
Centre Hospitalier de l'Université Laval (CHUL) Research Center, Quebec, QC, Canada.
J Lipid Res. 2024 Dec;65(12):100682. doi: 10.1016/j.jlr.2024.100682. Epub 2024 Oct 28.
Dietary supplementation with n-3 polyunsaturated fatty acids improves cognitive performance in several animal models of Alzheimer's disease (AD), an effect often associated with reduced amyloid-beta and/or tau pathologies. However, it remains unclear to what extent eicosapentaenoic (EPA) provides additional benefits compared to docosahexaenoic acid (DHA). Here, male and female 3xTg-AD mice were fed for 3 months (13-16 months of age) the following diets: (1) control (no DHA/EPA), (2) DHA (1.1g/kg) and low EPA (0.4g/kg), or (3) DHA (0.9g/kg) with high EPA (9.2g/kg). The DHA and DHA + EPA diets respectively increased DHA by 19% and 8% in the frontal cortex of 3xTg-AD mice, compared to controls. Levels of EPA, which were below the detection limit after the control diet, reached 0.14% and 0.29% of total brain fatty acids after the DHA and DHA + EPA diet, respectively. DHA and DHA + EPA diets lowered brain arachidonic acid levels and the n-6:n-3 docosapentaenoic acid ratio. Brain uptake of free C-DHA measured through intracarotid brain perfusion, but not of C-EPA, was lower in 3xTg-AD than in NonTg mice. DHA and DHA + EPA diets in 3xTg-AD mice reduced cortical soluble phosphorylated tau (pS202) (-34% high-DHA, -34% DHA + EPA, P < 0.05) while increasing p21-activated kinase (+58% and +83%, P < 0.001; respectively). High EPA intake lowered insoluble phosphorylated tau (-31% vs. DHA, P < 0.05). No diet effect on amyloid-beta levels was observed. In conclusion, dietary intake of DHA and EPA leads to differential changes in brain PUFA while altering cerebral biomarkers consistent with beneficial effects against AD-like neuropathology.
在阿尔茨海默病（AD）的几种动物模型中，补充n-3多不饱和脂肪酸可改善认知能力，这种作用通常与β-淀粉样蛋白和/或tau蛋白病变的减轻有关。然而，与二十二碳六烯酸（DHA）相比，二十碳五烯酸（EPA）在多大程度上能带来额外益处仍不清楚。在此，对雄性和雌性3xTg-AD小鼠在13 - 16月龄时喂食3个月以下饮食：（1）对照（无DHA/EPA），（2）DHA（1.1g/kg）和低剂量EPA（0.4g/kg），或（3）DHA（0.9g/kg）与高剂量EPA（9.2g/kg）。与对照组相比，DHA和DHA + EPA饮食分别使3xTg-AD小鼠额叶皮质中的DHA增加了19%和8%。对照饮食后低于检测限的EPA水平，在DHA和DHA + EPA饮食后分别达到脑总脂肪酸的0.14%和0.29%。DHA和DHA + EPA饮食降低了脑花生四烯酸水平以及n-6:n-3二十二碳五烯酸比例。通过颈内脑灌注测量，3xTg-AD小鼠脑对游离C-DHA的摄取低于非Tg小鼠，但对C-EPA的摄取无此差异。3xTg-AD小鼠的DHA和DHA + EPA饮食降低了皮质可溶性磷酸化tau（pS202）（高DHA组降低34%，DHA + EPA组降低34%，P < 0.05），同时增加了p21激活激酶（分别增加58%和83%，P < 0.001）。高剂量EPA摄入降低了不溶性磷酸化tau（与DHA组相比降低31%，P < 0.05）。未观察到饮食对β-淀粉样蛋白水平有影响。总之，饮食摄入DHA和EPA会导致脑多不饱和脂肪酸（PUFA）发生不同变化，同时改变与对抗AD样神经病理学有益作用一致的脑生物标志物。
