Alzheimer's disease (AD) is a neurodegenerative disorder without a known cure or effective treatment. Research has identified several modifiable risk factors and suggested preventative measures to reduce the risk of developing AD, including alterations in diet. Polyunsaturated fatty acids (PUFAs) have been shown to regulate inflammatory responses in the central nervous system (CNS), the main site of inflammation in AD. In the CNS, microglia are immune cells responsible for the maintenance of homeostasis. However, in AD, microglia can become adversely activated, causing them to release increased levels of cytotoxins and inflammatory mediators, including nitric oxide (NO) and monocyte-chemoattractant protein (MCP)-1. We assessed the effects of two PUFAs, α-linolenic acid (ALA) and linoleic acid (LA), on select microglial immune functions, since the effects of these dietary fatty acids on neuroimmune responses are not well characterized. In BV-2 mouse microglia activated with lipopolysaccharide (LPS), exposure to LA reduced NO secretion and inducible nitric oxide synthase (iNOS) levels, whereas exposure to ALA reduced NO without a corresponding reduction of iNOS. Neither ALA nor LA altered MCP-1 levels or cytotoxins released by THP-1 human microglia-like cells stimulated with a combination of LPS and interferon (IFN)-γ. Specific receptor antagonists were used to demonstrate that the inhibitory effect of LA on NO secretion did not depend on the free fatty acid receptor (FFAR) 1 or FFAR4. Furthermore, gas chromatography with a flame ionization detector (GC-FID) revealed that exposure to LA or ALA did not alter the fatty acid composition of BV-2 microglia. Our data indicate that regulation of select microglial immune functions by ALA and LA could be one of the mechanisms underlying the observed link between certain dietary patterns and AD, such as reduced risk of cognitive decline and dementia associated with the Mediterranean diet.

阿尔茨海默病 (AD) 是一种神经退行性疾病，没有已知的治愈方法或有效的治疗方法。研究已经确定了几个可改变的风险因素，并建议采取预防措施来降低患 AD 的风险，包括改变饮食。多不饱和脂肪酸 (PUFA) 已被证明可以调节中枢神经系统 (CNS) 的炎症反应，而中枢神经系统是 AD 炎症的主要部位。在中枢神经系统中，小胶质细胞是负责维持体内平衡的免疫细胞。然而，在 AD 中，小胶质细胞会被不利地激活，导致它们释放水平增加的细胞毒素和炎症介质，包括一氧化氮 (NO) 和单核细胞趋化蛋白 (MCP)-1。我们评估了两种 PUFA，α-亚麻酸 (ALA) 和亚油酸 (LA)，对特定小胶质细胞免疫功能的影响，因为这些膳食脂肪酸对神经免疫反应的影响还没有得到很好的表征。在用脂多糖 (LPS) 激活的 BV-2 小鼠小胶质细胞中，暴露于 LA 减少了 NO 分泌和诱导型一氧化氮合酶 (iNOS) 水平，而暴露于 ALA 减少了 NO，而 iNOS 没有相应减少。ALA 和 LA 都不会改变 MCP-1 水平或由 LPS 和干扰素 (IFN)-γ 组合刺激的 THP-1 人小胶质细胞样细胞释放的细胞毒素。特定受体拮抗剂用于证明 LA 对 NO 分泌的抑制作用不依赖于游离脂肪酸受体 (FFAR) 1 或 FFAR4。此外，带有火焰离子化检测器 (GC-FID) 的气相色谱显示，暴露于 LA 或 ALA 不会改变 BV-2 小胶质细胞的脂肪酸组成。