Fatty acid-binding protein 5 at the blood–brain barrier regulates endogenous brain docosahexaenoic acid levels and cognitive function

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Abstract

Fatty acid-binding protein 5 (FABP5) at the blood–brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA),a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition,the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+ and FABP5-/- mice using a battery of memory paradigms. FABP5-/- mice exhibited impaired working memory and short-term memory,and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood–brain barrier transport of DHA was assessed by measuring14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+ and FABP5-/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA,14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5-/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%,respectively,relative to those of FABP5+/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA,and that cognitive deficits observed in FABP5-/- mice are associated with reduced CNS access of DHA.

Original languageEnglish
Pages (from-to)11755-11767
Number of pages13
JournalJournal of Neuroscience
Volume36
Issue number46
DOIs
Publication statusPublished - 16 Nov 2016

Keywords

  • Blood–brain barrier
  • Brain microvascular endothelial cell
  • Cognitive function
  • Docosahexaenoic acid
  • Fatty acid-binding protein

Cite this

@article{098f15e0d24d4df0b2ee08c3c06b5974,
title = "Fatty acid-binding protein 5 at the blood–brain barrier regulates endogenous brain docosahexaenoic acid levels and cognitive function",
abstract = "Fatty acid-binding protein 5 (FABP5) at the blood–brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA),a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition,the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+ and FABP5-/- mice using a battery of memory paradigms. FABP5-/- mice exhibited impaired working memory and short-term memory,and these cognitive deficits were associated with a 14.7 ± 5.7{\%} reduction in endogenous brain DHA levels. The role of FABP5 in the blood–brain barrier transport of DHA was assessed by measuring14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+ and FABP5-/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA,14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5-/- mice was reduced by 48.4 ± 14.5{\%} and 14.0 ± 4.2{\%},respectively,relative to those of FABP5+/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA,and that cognitive deficits observed in FABP5-/- mice are associated with reduced CNS access of DHA.",
keywords = "Blood–brain barrier, Brain microvascular endothelial cell, Cognitive function, Docosahexaenoic acid, Fatty acid-binding protein",
author = "Yijun Pan and Short, {Jennifer L.} and Choy, {Kwok H C} and Zeng, {Annie X.} and Marriott, {Philip J.} and Yuji Owada and Scanlon, {Martin J.} and Porter, {Christopher J.H.} and Nicolazzo, {Joseph A.}",
year = "2016",
month = "11",
day = "16",
doi = "10.1523/JNEUROSCI.1583-16.2016",
language = "English",
volume = "36",
pages = "11755--11767",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
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TY - JOUR

T1 - Fatty acid-binding protein 5 at the blood–brain barrier regulates endogenous brain docosahexaenoic acid levels and cognitive function

AU - Pan, Yijun

AU - Short, Jennifer L.

AU - Choy, Kwok H C

AU - Zeng, Annie X.

AU - Marriott, Philip J.

AU - Owada, Yuji

AU - Scanlon, Martin J.

AU - Porter, Christopher J.H.

AU - Nicolazzo, Joseph A.

PY - 2016/11/16

Y1 - 2016/11/16

N2 - Fatty acid-binding protein 5 (FABP5) at the blood–brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA),a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition,the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+ and FABP5-/- mice using a battery of memory paradigms. FABP5-/- mice exhibited impaired working memory and short-term memory,and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood–brain barrier transport of DHA was assessed by measuring14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+ and FABP5-/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA,14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5-/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%,respectively,relative to those of FABP5+/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA,and that cognitive deficits observed in FABP5-/- mice are associated with reduced CNS access of DHA.

AB - Fatty acid-binding protein 5 (FABP5) at the blood–brain barrier contributes to the brain uptake of docosahexaenoic acid (DHA),a blood-derived polyunsaturated fatty acid essential for maintenance of cognitive function. Given the importance of DHA in cognition,the aim of this study was to investigate whether deletion of FABP5 results in cognitive dysfunction and whether this is associated with reduced brain endothelial cell uptake of exogenous DHA and subsequent attenuation in the brain levels of endogenous DHA. Cognitive function was assessed in male and female FABP5+/+ and FABP5-/- mice using a battery of memory paradigms. FABP5-/- mice exhibited impaired working memory and short-term memory,and these cognitive deficits were associated with a 14.7 ± 5.7% reduction in endogenous brain DHA levels. The role of FABP5 in the blood–brain barrier transport of DHA was assessed by measuring14C-DHA uptake into brain endothelial cells and capillaries isolated from FABP5+/+ and FABP5-/- mice. In line with a crucial role of FABP5 in the brain uptake of DHA,14C-DHA uptake into brain endothelial cells and brain capillaries of FABP5-/- mice was reduced by 48.4 ± 14.5% and 14.0 ± 4.2%,respectively,relative to those of FABP5+/+ mice. These results strongly support the hypothesis that FABP5 is essential for maintaining brain endothelial cell uptake of DHA,and that cognitive deficits observed in FABP5-/- mice are associated with reduced CNS access of DHA.

KW - Blood–brain barrier

KW - Brain microvascular endothelial cell

KW - Cognitive function

KW - Docosahexaenoic acid

KW - Fatty acid-binding protein

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U2 - 10.1523/JNEUROSCI.1583-16.2016

DO - 10.1523/JNEUROSCI.1583-16.2016

M3 - Article

VL - 36

SP - 11755

EP - 11767

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 46

ER -