Pan Yijun, Choy Kwok H C, Marriott Philip J, Chai Siew Y, Scanlon Martin J, Porter Christopher J H, Short Jennifer L, Nicolazzo Joseph A
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Vic., Australia.
J Neurochem. 2018 Jan;144(1):81-92. doi: 10.1111/jnc.14249.
Lower levels of the cognitively beneficial docosahexaenoic acid (DHA) are often observed in Alzheimer's disease (AD) brains. Brain DHA levels are regulated by the blood-brain barrier (BBB) transport of plasma-derived DHA, a process facilitated by fatty acid-binding protein 5 (FABP5). This study reports a 42.1 ± 12.6% decrease in the BBB transport of C-DHA in 8-month-old AD transgenic mice (APPswe,PSEN1∆E9) relative to wild-type mice, associated with a 34.5 ± 6.7% reduction in FABP5 expression in isolated brain capillaries of AD mice. Furthermore, short-term spatial and recognition memory deficits were observed in AD mice on a 6-month n-3 fatty acid-depleted diet, but not in AD mice on control diet. This intervention led to a dramatic reduction (41.5 ± 11.9%) of brain DHA levels in AD mice. This study demonstrates FABP5 deficiency and impaired DHA transport at the BBB are associated with increased vulnerability to cognitive deficits in mice fed an n-3 fatty acid-depleted diet, in line with our previous studies demonstrating a crucial role of FABP5 in BBB transport of DHA and cognitive function.
在阿尔茨海默病（AD）患者的大脑中，通常会观察到对认知有益的二十二碳六烯酸（DHA）水平较低。大脑中的DHA水平受血浆来源的DHA通过血脑屏障（BBB）转运的调节，这一过程由脂肪酸结合蛋白5（FABP5）促进。本研究报告称，与野生型小鼠相比，8月龄AD转基因小鼠（APPswe,PSEN1∆E9）中C-DHA的血脑屏障转运减少了42.1±12.6%，这与AD小鼠分离脑微血管中FABP5表达降低34.5±6.7%有关。此外，在6个月n-3脂肪酸缺乏饮食的AD小鼠中观察到短期空间和识别记忆缺陷，但在对照饮食的AD小鼠中未观察到。这种干预导致AD小鼠脑DHA水平显著降低（41.5±11.9%）。本研究表明，FABP5缺乏和血脑屏障处DHA转运受损与喂食n-3脂肪酸缺乏饮食的小鼠认知缺陷易感性增加有关，这与我们之前的研究一致，即FABP5在血脑屏障DHA转运和认知功能中起关键作用。
