Blood–brain barrier and brain fatty acid uptake: Role of arachidonic acid and <scp>PGE</scp><sub>2</sub>

Murphy, Eric J.

doi:10.1111/jnc.13289

Cited by 14 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PUFAs (≈Cholesterylesters) take an important place (13.61%) as well as their carriers the LPC lipid compound (5.64%) [13][14][15][16]. Interestingly, both omega-3 "fish oil" FA EPA and DHA are found in rather high concentrations respectively 0.277% and 0.258% respectively in blood plasma but not in the brain.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

Ginneken¹,

Meerveld²,

Verheij³

et al. 2017

J Bioanal Biomed

View full text Add to dashboard Cite

What is known about the brain is a scanty amount of information despite its importance in human evolution. Here we perform based on a holistic Systems Biology lipidomics approach an attempt describing the brain biochemical lipid composition based on the homogenate of a part (gyrus) of the neocortex of post mortem material of the "Dutch Brain Bank" with LCMS techniques. From evolutionary perception the occurrence of the "fish oils" in blood and/ or brain is interesting and their ability to pass the Blood-Brain Barrier (BBB). Both omega-3 "fish oil" Fatty Acids (FA) Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA). EPA and DHA are found in rather high concentrations respectively 0.277% and 0.258% respectively in blood plasma but not in the brain. EPA is not found in grey or white neocortex matter so probably it cannot pass the BBB while this is the case for DHA giving values of respectively ≈0.00015% while Triacylglycerols (TGs) are the major constituent of the human brain with a mean value of the neocortex of ≈72%. We finally conclude the TGs have played a major role in the process of human brain growth and encephalization during course of evolution. the occurrence of the "fish oils" in blood and/or brain is interesting and their ability to pass the BBB. Based on our observations we open the debate which lipid class-the PUFAs vs. the TGs-have played a major unambiguously role in the process of human brain growth and encephalization. Our initial hypothesis is that the TGs have played a major role in human brain skull expansion or encephalization and that the "fish oil" DHA is a tiny fraction of the FA in the brain and is of minor importance of human encephalization. Material and MethodsWe quantified and qualified the rearrangement and repartitioning of these fat stores in the brain of male post mortem subjects (Control n=8; 73.5 ± 10.5 years; Type-2 diabetes n=8; 77.3 ± 7.2 years) which were obtained from the 'Netherlands Brain Bank' . We quantified 109 lipid compounds based on mass and polarity using LCMS methods as described earlier [5,12]. Briefly, we followed next protocol.Brain-tissue: Human Brain tissue was obtained from the "Netherlands Brain Bank". Causes of death causes are presented in Table 1 [12]. Time of post mortem dissection varied between 4.4 and 24.5 h (Table 1) [12]. The region of post mortem collection of the tissue material was mainly the cortex (Table 1) [12]. Visually, a clear separation could be made between grey and white matter in the cortex. A tissue homogenate of the brain tissue (grey or white; ~10% wet weight/volume) in Phosphate-Buffered Saline (PBS) was made with the Mini-beat Beater.Blood plasma: Blood was centrifuged at 8000 × g for 5 min. The plasma was aliquoted and stored at -80ºC at the "Netherlands Brain Bank" pending analysis LC-MS: Lipids and free fatty acids (FFA) were analyzed with electrospray LC-MS as earlier performed. For blood plasma 10 µl samples were extracted with 300 µl of isopropanol (IPA) containing several internal standards (IS: C17:0 lysopho...

show abstract

Section: Resultsmentioning

confidence: 99%

“…states and this might be stimulated by a physiological level of Arachidonic Acid (ARA) [13]. But probably many other compounds of mainly the Cholesteryl fraction (PUFAs) are involved, and for this reasoning we will elucidate this topic related to optional passive/active carriers in the BBB.…”

Section: Discussionmentioning

confidence: 99%

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

Ginneken¹,

Meerveld²,

Verheij³

et al. 2017

J Bioanal Biomed

View full text Add to dashboard Cite

show abstract

“…The study of [10] demonstrates that the intracellular carrier protein fatty acid-binding protein 5 (FABP5) binds to DHA and is involved in the brain endothelial cell uptake and subsequent BBB transport of DHA, confirming the importance of this cytoplasmic carrier protein in the CNS exposure of this PUFA essential for neuronal function The importance of FA for the developing and adult brain has been recently reviewed [22]. In addition, recent investigations are indicative this might be stimulated by a physiological level of arachidonic acid (ARA) [23] -but probably many other compounds-that could be associated with many different physiological and pathophysiological states. In these studies an increased model of permeability model of the human blood brain barrier (BBB) in the absence of cytokines was suggested [23,24].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, recent investigations are indicative this might be stimulated by a physiological level of arachidonic acid (ARA) [23] -but probably many other compounds-that could be associated with many different physiological and pathophysiological states. In these studies an increased model of permeability model of the human blood brain barrier (BBB) in the absence of cytokines was suggested [23,24].…”

Section: Discussionmentioning

confidence: 99%

“Brain steatosis” in an obese mouse model during cycles of Famine and Feast the underestimated role of fat (WAT) in brain volume formation

Ginneken¹,

Vries²,

Verheij³

et al. 2017

Integr Mol Med

View full text Add to dashboard Cite

Objective: Explain the observation of the the mechanism of an "overgrown brain" in a C57bl6 mouse model after exposure of juvenile individuals for 40 days to a High Fat diet based on bovine lard.Methods: 8-12 weeks old C57Bl6 mice were fed for 40 days a high-fat diet (+025% cholesterol 45% energy from bovine lard). With LC-MS techniques we measured Cholesteryl esters(ChE), lysophosphatidyl-cholines (LPC), phosphatidylcholine (PC), sphingomyelin (SPM) and Triacylglycerol's (TG) in brain tissue after 40 days of exposure to a High Fat diet or nutritional intervention of two days starvation. Results:Major observation was that mainly unsaturated Very Long Chain Fatty Acids (TGs) of the C:50, C:52, C:54 and C56 TGs fraction were extremely accumulated in this HF-diet and were strongly correlated with the TGs with the HF-diet obese C57BL6 whole brain fraction (correlation coefficient r2=07.60 in comparison to control chow r2= 0.264). In addition, "brain steatosis" in the HF-diet group was also caused by a non-significant 135% increase of Docosahexaenoic Acid ([DHA] C22:6Ω3) in the HF-diet group in the brain. LPC and SPM were strongly significantly decreased in the starvation group (P<0.0001), followed by a strong decrease of PC and PE (P<0.007), followed by the DG fraction (P<0.017). In addition, ChE strongly significantly increased in the HF-diet group (P<0.001).Conclusions: From our observations we can conclude a juvenile rodent study showed in a by bovine lard induced obesity model an "overgrown brain" mainly by the accumulation of triacylglycerols (TGs). These observations of "brain steatosis" in a C57bl6 mouse model after a High Fat diet based on bovine lard in combination with the literature data of the anatomically found strict correlation between maternal Body Mass Index (BMI) and head circumference of new-born elevates our observations to the evolutionary research area of human encephalization.

show abstract

“…It has been suggested that some fatty acids, like erucic acid (308, 309), suffer metabolic changes as they cross the BBB, whereas others do not (310, 311). Studies indicate that lipoproteins are hydrolyzed as they cross the BBB by the enzyme lipoprotein lipase associated to the membrane of endothelial cells (312–316).…”

Section: Functions Of Non-neuronal Cellsmentioning

confidence: 99%

Non-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals

et al. 2017

View full text Add to dashboard Cite

Although the brain is composed of numerous cell types, neurons have received the vast majority of attention in the attempt to understand how this organ functions. Neurons are indeed fundamental but, in order for them to function correctly, they rely on the surrounding “non-neuronal” cells. These different cell types, which include glia, epithelial cells, pericytes, and endothelia, supply essential substances to neurons, in addition to protecting them from dangerous substances and situations. Moreover, it is now clear that non-neuronal cells can also actively participate in determining neuronal signaling outcomes. Due to the increasing problem of obesity in industrialized countries, investigation of the central control of energy balance has greatly increased in attempts to identify new therapeutic targets. This has led to interesting advances in our understanding of how appetite and systemic metabolism are modulated by non-neuronal cells. For example, not only are nutrients and hormones transported into the brain by non-neuronal cells, but these cells can also metabolize these metabolic factors, thus modifying the signals reaching the neurons. The hypothalamus is the main integrating center of incoming metabolic and hormonal signals and interprets this information in order to control appetite and systemic metabolism. Hence, the factors transported and released from surrounding non-neuronal cells will undoubtedly influence metabolic homeostasis. This review focuses on what is known to date regarding the involvement of different cell types in the transport and metabolism of nutrients and hormones in the hypothalamus. The possible involvement of non-neuronal cells, in particular glial cells, in physiopathological outcomes of poor dietary habits and excess weight gain are also discussed.

show abstract

Blood–brain barrier and brain fatty acid uptake: Role of arachidonic acid and PGE₂

Abstract: Read the full article 'Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E 2 activation of EP 3 and EP 4 receptors' on page 867.

Cited by 14 publications

References 33 publications

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

“Brain steatosis” in an obese mouse model during cycles of Famine and Feast the underestimated role of fat (WAT) in brain volume formation

Non-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals

Contact Info

Product

Resources

About

Blood–brain barrier and brain fatty acid uptake: Role of arachidonic acid and PGE2

Abstract: Read the full article 'Exogenous arachidonic acid mediates permeability of human brain microvessel endothelial cells through prostaglandin E 2 activation of EP 3 and EP 4 receptors' on page 867.

Cited by 14 publications

References 33 publications

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

On the Futile Existence of DHA, None of EPA and the Predominant Role of the Triacylglycerols (TGs) in the Post Mortem Human Brain: An LCMS Study with Evolutionary Implications

“Brain steatosis” in an obese mouse model during cycles of Famine and Feast the underestimated role of fat (WAT) in brain volume formation

Non-Neuronal Cells in the Hypothalamic Adaptation to Metabolic Signals

Contact Info

Product

Resources

About

Blood–brain barrier and brain fatty acid uptake: Role of arachidonic acid and PGE₂