1. Reduced blood-brain barrier expression of fatty acid-binding protein 5 is associated with increased vulnerability of APP/PS1 mice to cognitive deficits from low omega-3 fatty acid diets.
- Author
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Pan Y, Choy KHC, Marriott PJ, Chai SY, Scanlon MJ, Porter CJH, Short JL, and Nicolazzo JA
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease metabolism, Amyloid beta-Protein Precursor genetics, Amyloid beta-Protein Precursor metabolism, Animals, Brain Chemistry, Cognition Disorders genetics, Cognition Disorders metabolism, Dietary Fats administration & dosage, Docosahexaenoic Acids deficiency, Escherichia coli Proteins, Fatty Acid-Binding Proteins biosynthesis, Fatty Acids, Omega-3 deficiency, Female, Humans, Male, Maze Learning, Memory Disorders etiology, Memory Disorders genetics, Memory Disorders metabolism, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Missense, Neoplasm Proteins biosynthesis, Polysaccharide-Lyases, Presenilin-1 genetics, Presenilin-1 metabolism, Recognition, Psychology, Recombinant Fusion Proteins metabolism, Blood-Brain Barrier, Cognition Disorders etiology, Docosahexaenoic Acids pharmacokinetics, Fatty Acid-Binding Proteins physiology, Neoplasm Proteins physiology
- Abstract
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
14 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., (© 2017 International Society for Neurochemistry.)- Published
- 2018
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