LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4.
LPC-DHA/EPA-Enriched Diets Increase Brain DHA and Modulate Behavior in Mice That Express Human APOE4.
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DOI：
10.3389/fnins.2021.690410
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发表时间：
2021
影响因子：
4.3
通讯作者：
Tai LM
中科院分区：
文献类型：
--
作者：
Scheinman SB;Sugasini D;Zayed M;Yalagala PCR;Marottoli FM;Subbaiah PV;Tai LM
与APOE 3相比，APOE 4与更大的年龄相关性认知衰退和更高的神经退行性疾病风险相关。因此，开发针对APOE基因型调节过程的补充剂可以为老龄化人口提供很大的益处。有证据表明APOE基因型与二十二碳六烯酸（DHA）之间存在联系;然而，目前DHA补充剂的临床研究对痴呆症产生了负面影响。目前DHA补充剂缺乏有益效果可能与有限的生物利用度有关，因为用于大脑摄取的DHA的最佳形式是溶血磷脂酰胆碱（LPC）-DHA。我们之前开发了一种通过脂肪酶处理（LT-磷虾油）富集磷虾油中LPC-DHA含量的方法，与未处理的磷虾油相比，野生型小鼠脑DHA水平的富集程度高出五倍。在此，我们评估了对照饮食、含磷虾油的饮食或含LT-磷虾油的饮食在APOE 3-和APOE 4-靶向替代小鼠（APOE-TR小鼠;从4至12个月大接受治疗）中的作用。我们发现APOE 4-TR小鼠血浆和海马中的DHA水平较低，LT-磷虾油增加了APOE 3-和APOE 4-TR小鼠血浆和海马中的DHA水平。在APOE 4-TR小鼠中，LT-磷虾油治疗导致突触囊泡蛋白SV 2A水平更高，并改善了新物体识别测试的性能。总之，我们的数据表明，富含LPC-DHA/EPA的磷虾油可以增加表达APOE 4的小鼠的大脑DHA并改善记忆相关行为。因此，长期使用LT-磷虾油补充剂可以在一定程度上防止与年龄相关的神经退行性变。
Compared with APOE3, APOE4 is associated with greater age-related cognitive decline and higher risk of neurodegenerative disorders. Therefore, development of supplements that target APOE genotype-modulated processes could provide a great benefit for the aging population. Evidence suggests a link between APOE genotype and docosahexaenoic acid (DHA); however, clinical studies with current DHA supplements have produced negative results in dementia. The lack of beneficial effects with current DHA supplements may be related to limited bioavailability, as the optimal form of DHA for brain uptake is lysophosphatidylcholine (LPC)-DHA. We previously developed a method to enrich the LPC-DHA content of krill oil through lipase treatment (LT-krill oil), which resulted in fivefold higher enrichment in brain DHA levels in wild-type mice compared with untreated krill oil. Here, we evaluated the effect of a control diet, diet containing krill oil, or a diet containing LT-krill oil in APOE3- and APOE4-targeted replacement mice (APOE-TR mice; treated from 4 to 12 months of age). We found that DHA levels in the plasma and hippocampus are lower in APOE4-TR mice and that LT-krill oil increased DHA levels in the plasma and hippocampus of both APOE3- and APOE4-TR mice. In APOE4-TR mice, LT-krill oil treatment resulted in higher levels of the synaptic vesicle protein SV2A and improved performance on the novel object recognition test. In conclusion, our data demonstrate that LPC-DHA/EPA-enriched krill oil can increase brain DHA and improve memory-relevant behavior in mice that express APOE4. Therefore, long-term use of LT-krill oil supplements may on some level protect against age-related neurodegeneration.
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