Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.
J Neurosci Res. 2010 Apr;88(5):1026-40. doi: 10.1002/jnr.22266.
Epidemiological and clinical trial findings suggest that consumption of docosahexaenoic acid (DHA) lowers the risk of Alzheimer's disease (AD). We examined the effects of short-term (3 months) DHA enriched diet on plaque deposition and synaptic defects in forebrain of young APPswe/PS1 Delta E9 transgenic (tg) and non-transgenic (ntg) mice. Gas chromatography revealed a significant increase in DHA concomitant with a decrease of arachidonic acid in both brain and liver in mice fed with DHA. Female tg mice consumed relatively more food daily than ntg female mice, independent of diet. Plaque load was significantly reduced in the cortex, ventral hippocampus and striatum of female APPswe/PS1 Delta E9 tg mice on DHA diet compared to female tg mice on control diet. Immunoblot quantitation of the APOE receptor, LR11, which is involved in APP trafficking and A beta production, were unchanged in mice on DHA or control diets. Moreover drebrin levels were significantly increased in the hippocampus of tg mice on the DHA diet. Finally, in vitro DHA treatment prevented amyloid toxicity in cell cultures. Our findings support the concept that increased DHA consumption may play and important role in reducing brain insults in female AD patients.
流行病学和临床试验的结果表明，二十二碳六烯酸（DHA）的摄入可以降低阿尔茨海默病（AD）的风险。我们研究了短期（3 个月）富含 DHA 的饮食对年轻 APPswe/PS1 Delta E9 转基因（tg）和非转基因（ntg）小鼠大脑前额叶斑块沉积和突触缺陷的影响。气相色谱显示，DHA 喂养的小鼠大脑和肝脏中的 DHA 显著增加，同时花生四烯酸减少。无论饮食如何，雌性 tg 小鼠每天的食物摄入量都明显高于雌性 ntg 小鼠。与接受对照饮食的雌性 tg 小鼠相比，接受 DHA 饮食的雌性 APPswe/PS1 Delta E9 tg 小鼠大脑皮层、腹侧海马和纹状体的斑块负荷明显减少。LR11 是 APP 转运和 Aβ产生所涉及的 APOE 受体，其在接受 DHA 或对照饮食的小鼠中的免疫印迹定量没有变化。此外，在 DHA 饮食的 tg 小鼠的海马体中 drebrin 水平显著增加。最后，体外 DHA 处理可预防细胞培养物中的淀粉样毒性。我们的研究结果支持这样一种观点，即增加 DHA 的摄入可能在减少女性 AD 患者大脑损伤方面发挥重要作用。
