1. Department of Pharmacology, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, China;2. Department of Pathology, The First Affiliated Hospital of Sun Yat‐sen University, Guangzhou, China;3. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, The Sixth Affiliated Hospital of Sun Yat‐sen University, Guangzhou, China;4. Guangzhou Cellprotek Pharmaceutical Co. ltd., Science City, Guangzhou, China;5. Department of Biochemistry, Zhongshan School of Medicine, Sun Yat‐sen University, Guangzhou, China
Abstract:
The cytoplasmic trafficking of docosahexaenoic acid (DHA ), a cognitively beneficial fatty acid, across the blood–brain barrier (BBB ) is governed by fatty acid‐binding protein 5 (FABP 5). Lower levels of brain DHA have been observed in Alzheimer's disease (AD ), which is associated with diminished BBB expression of FABP 5. Therefore, up‐regulating FABP 5 expression at the BBB may be a novel approach for enhancing BBB transport of DHA in AD . DHA supplementation has been shown to be beneficial in various mouse models of AD , and therefore, the aim of this study was to determine whether DHA has the potential to up‐regulate the BBB expression of FABP 5, thereby enhancing its own uptake into the brain. Treating human brain microvascular brain endothelial (hCMEC /D3) cells with the maximum tolerable concentration of DHA (12.5 μM) for 72 h resulted in a 1.4‐fold increase in FABP 5 protein expression. Associated with this was increased expression of fatty acid transport proteins 1 and 4. To study the impact of dietary DHA supplementation, 6‐ to 8‐week‐old C57BL /6 mice were fed with a control diet or a DHA ‐enriched diet for 21 days. Brain microvascular FABP 5 protein expression was up‐regulated 1.7‐fold in mice fed the DHA ‐enriched diet, and this was associated with increased brain DHA levels (1.3‐fold). Despite an increase in brain DHA levels, reduced BBB transport of 14C‐DHA was observed over a 1 min perfusion, possibly as a result of competitive binding to FABP 5 between dietary DHA and 14C‐DHA . This study has demonstrated that DHA can increase BBB expression of FABP 5, as well as fatty acid transporters, overall increasing brain DHA levels.
