Maternal Supply of Both Arachidonic and Docosahexaenoic Acids Is Required for Optimal Neurodevelopment

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural–functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, the importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA, in supporting the optimal brain development and growth and functional roles in the brain.

Download Full-text

Maternal Supply of Both Arachidonic and Docosahexaenoic Acids is Required for Optimal Neurodevelopment

10.20944/preprints202104.0665.v3 ◽

2021 ◽

Author(s):

Sanjay Basak ◽

Rahul Mallick ◽

Antara Banerjee ◽

Surajit Pathak ◽

Asim K. Duttaroy

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Arachidonic Acid ◽

Cerebral Cortex ◽

Brain Development ◽

Rapid Rate ◽

Postnatal Brain ◽

Functional Roles ◽

The Brain ◽

Docosahexaenoic Acids

During the last trimester of gestation and for the first 18 months after birth, both docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) are preferentially deposited within the cerebral cortex at a rapid rate. Although, the structural and functional roles of DHA in brain development are well investigated, similar roles of ARA are not well documented. The mode of action of these two fatty acids and their derivatives at different structural-functional roles and their levels in the gene expression and signaling pathways of the brain have been continuously emanating. In addition to DHA, importance of ARA has been much discussed in recent years for fetal and postnatal brain development and the maternal supply of ARA and DHA. These fatty acids are also involved in various brain developmental processes; however, their mechanistic cross talks are not clearly known yet. This review describes the importance of ARA, in addition to DHA to support the optimal brain development and growth and functional roles in the brain.

Download Full-text

Does Maternal Arachidonic Acid Influence the Neurodevelopmental Effects of Docosahexaenoic Acid?

10.20944/preprints202104.0665.v2 ◽

2021 ◽

Author(s):

Sanjay Basak ◽

Rahul Mallick ◽

Antara Banerjee ◽

Surajit Pathak ◽

Asim K. Duttaroy

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Cerebral Cortex ◽

Docosahexaenoic Acid ◽

Mechanisms Of Action ◽

Structural Function ◽

Rapid Rate ◽

Functional Roles ◽

The Brain ◽

Neurodevelopmental Effects

During the last trimester of gestation and for the first 18 months after birth, docosahexaenoic acid,22:6n-3 (DHA) and arachidonic acid,20:4n-6 (ARA) deposited within the cerebral cortex at a rapid rate. The mode of action of these two fatty acids and their derivatives at different structural-function and signaling pathways levels in the brain have been continuously emanating. These fatty acids are also involved in various brain developmental processes; however, their mechanisms of action are not yet well known. Recent data suggest that there may be a need for a balanced proportion of ARA and DHA in infant formula due to their complementary benefits. This review describes the importance of maternal preferential transfer of ARA and DHA to support the infant's optimal brain development and growth and functional roles in the brain.

Download Full-text

Does Maternal Arachidonic Acid Influence the Neurodevelopmental Effects of Docosahexaenoic Acid?

10.20944/preprints202104.0665.v1 ◽

2021 ◽

Author(s):

Asim K. Duttaroy

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Cerebral Cortex ◽

Docosahexaenoic Acid ◽

Mechanisms Of Action ◽

Structural Function ◽

Rapid Rate ◽

Functional Roles ◽

The Brain ◽

Neurodevelopmental Effects

Download Full-text

Entry of polyunsaturated fatty acids into the brain: evidence that high-density lipoprotein-induced methylation of phosphatidylethanolamine and phospholipase A2 are involved

Biochemical Journal ◽

10.1042/bj3160805 ◽

1996 ◽

Vol 316 (3) ◽

pp. 805-811 ◽

Cited By ~ 22

Author(s):

Valérie MAGRET ◽

Latifa ELKHALIL ◽

Françoise NAZIH-SANDERSON ◽

Françoise MARTIN ◽

Jean-Marie BOURRE ◽

...

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Polyunsaturated Fatty Acids ◽

High Density Lipoprotein ◽

Phospholipase A2 ◽

Density Lipoprotein ◽

Bovine Brain ◽

High Density ◽

Close Relationship ◽

The Brain

The conversion of phosphatidylethanolamine (PE) into phosphatidylcholine (PC) by a sequence of three transmethylation reactions is shown to be stimulated by the apolipoprotein E-free subclass of high-density lipoprotein (HDL3) in isolated bovine brain capillary (BBC) membranes. HDL3-induced stimulation of BBC membranes pulsed with [methyl-14C]methionine causes a transient increase in each methylated phospholipid, i.e. phosphatidyl-N-monomethylethanolamine (PMME), phosphatidyl-NN-dimethylethanolamine (PDME) and PC. PC substrate arising from the activation of PE N-methyltransferase (PEMT) is hydrolysed by a phospholipase A2 (PLA2), as demonstrated by the accumulation of lysophosphatidylcholine (lyso-PC). When PE containing [14C]arachidonic acid in the sn-2 position ([14C]PAPE) is incorporated into BBC membranes, HDL3 stimulation induces the formation of PMME, PDME, PC and lyso-PC and the release of [14C]arachidonic acid, which correlates with the previous production of lyso-PC, suggesting that HDL3 stimulates a PLA2 that can release polyunsaturated fatty acids (PUFA). Both PEMT and PLA2 activities depend on a HDL3 concentration in the range 0–50 μg/ml and are strictly dependent on HDL3 binding, because HDL3 modified by tetranitromethane is no longer able to bind to specific receptors and to trigger PEMT and PLA2 activation. Moreover, HDL3 prelabelled with [14C]PAPE can stimulate PDME and lyso-PC synthesis in BBC membranes in the presence of S-adenosylmethionine, suggesting that HDL3 can supply BBC membranes in polyunsaturated PE and can activate enzymes involved in PE N-methylation and PUFA release. The results support the hypothesis of a close relationship between HDL3 binding, PE methylation and PUFA release, and suggest that the PC pool arising from PE could be used as a pathway for the supply of PUFA to the brain.

Download Full-text

Characterization of plasma unsaturated lysophosphatidylcholines in human and rat

Biochemical Journal ◽

10.1042/bj3450061 ◽

1999 ◽

Vol 345 (1) ◽

pp. 61-67 ◽

Cited By ~ 114

Author(s):

Martine CROSET ◽

Nicole BROSSARD ◽

Anne POLETTE ◽

Michel LAGARDE

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Rat Plasma ◽

Arachidonic Acid Content ◽

Tissue Uptake ◽

Membrane Phospholipids ◽

Esterified Fatty Acids ◽

The Brain ◽

Group Shift

Unsaturated lysophosphatidylcholines (lysoPtdCho) bound to albumin circulate in blood plasma and seem to be a novel transport system for carrying polyunsaturated fatty acids (PUFA) to tissues that are rich in these fatty acids, such as the brain. The potential of these lysoPtdCho as a significant source of PUFA for cells has been assessed by comparing their plasma concentration with that of unsaturated non-esterified fatty acids (NEFA) bound to albumin. In humans, the PUFA concentration was 25.9±3.1 nmol/ml for these lysoPtdCho, compared with 33.4±9.6 nmol/ml for NEFA; in rats the equivalent values are 14.2±0.6 and 13.1±1.1 nmol/ml respectively (means±S.E.M.). The lysoPtdCho arachidonic acid content was 2-fold (human) and 5-fold (rat) higher than that of NEFA. In human and rat plasma, unsaturated lysoPtdCho were associated mainly with albumin rather than lipoproteins. The rate and extent of the acyl group shift from the sn-2 to sn-1 position of these lysoPtdCho were studied by the incubation of 1-lyso,2-[14C]C18:2n-6-glycerophosphocholine (GPC) with plasma. The rapid isomerization of this lipid occurred at pH 7 (20% isomerization within 2 min) and was not prevented by its association with albumin. The position of the acyl group in the lysoPtdCho circulating in plasma was studied by collecting blood directly in organic solvents containing 1-lyso,2-[14C]C18:2n-6-GPC as a marker of isomerization that occurred during sampling and analysis. Approx. 50% of the PUFA was located at the sn-2 position, demonstrating that substantial concentrations of 2-acyl-lysoPtdCho are present in plasma and are available for tissue uptake, where they can be reacylated at the sn-1 position to form membrane phospholipids.

Download Full-text

Gene expression levels of DNA methyltransferase enzymes in Shank3-deficient mouse model of autism during early development

Endocrine Regulations ◽

10.2478/enr-2021-0025 ◽

2021 ◽

Vol 55 (4) ◽

pp. 234-237

Author(s):

Annamaria Srancikova ◽

Alexandra Reichova ◽

Zuzana Bacova ◽

Jan Bakos

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Brain Development ◽

Early Development ◽

Molecular Mechanisms ◽

Altered Expression ◽

Expression Levels ◽

The Brain ◽

Deficient Mice ◽

Gene Expression Levels

Abstract Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

Download Full-text

The Effect of Polyunsaturated Fatty Acids on Endothelial Cells and Their Production of Prostacyclin, Thromboxane and Platelet Inhibitory Activity

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665307 ◽

1983 ◽

Vol 50 (04) ◽

pp. 762-767 ◽

Cited By ~ 26

Author(s):

Jan H Brox ◽

Arne Nordøy

Keyword(s):

Fatty Acids ◽

Endothelial Cells ◽

Arachidonic Acid ◽

Endothelial Cell ◽

Polyunsaturated Fatty Acids ◽

Linolenic Acid ◽

Inhibitory Activity ◽

Primary Cultures ◽

Cell Monolayers ◽

Docosahexaenoic Acids

SummaryPrimary cultures of human endothelial cell monolayers were incubated with albumin-bound fatty acids of the ω-3 and ω-6 families for a maximum of 24 hrs, to investigate the production of 6-keto-PGF1α, TXB2 and platelet inhibitory activity (PIA). Arachidonic acid was a potent stimulator of all parameters. The release of 6-keto-PGF1α was significantly reduced by equimolar concentrations of linoleic, dihomogamma linolenic and eicosapentaenoic acids, but not by linolenic acid. PIA was not similarity affected.Dihomogamma linolenic add was also a weak stimulator of 6- keto-PGF1α and PIA, but reduced the content of both in the cells after 24 hrs. Eicosapentaenoic and docosahexaenoic acids both depressed 6-keto-PGF1α production but PIA was maintained after 24 hrs. Indomethacin always blocked 6-keto-PGF1α and PIA production. None of the effects correlated to release of 51CR from prelabelled cells.

Download Full-text

The effects of n-6 polyunsaturated fatty acid deprivation on the inflammatory gene response to lipopolysaccharide in the mouse hippocampus

Journal of Neuroinflammation ◽

10.1186/s12974-019-1615-0 ◽

2019 ◽

Vol 16 (1) ◽

Cited By ~ 3

Author(s):

Shoug M. Alashmali ◽

Lin Lin ◽

Marc-Olivier Trépanier ◽

Giulia Cisbani ◽

Richard P. Bazinet

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Diet Group ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Left Lateral Ventricle ◽

Gene Response ◽

Mouse Hippocampus ◽

Total Fatty Acids ◽

The Brain

Abstract Background Neuroinflammation is thought to contribute to psychiatric and neurological disorders such as major depression and Alzheimer’s disease (AD). N-6 polyunsaturated fatty acids (PUFA) and molecules derived from them, including linoleic acid- and arachidonic acid-derived lipid mediators, are known to have pro-inflammatory properties in the periphery; however, this has yet to be tested in the brain. Lowering the consumption of n-6 PUFA is associated with a decreased risk of depression and AD in human observational studies. The purpose of this study was to investigate the inflammation-modulating effects of lowering dietary n-6 PUFA in the mouse hippocampus. Methods C57BL/6 male mice were fed either an n-6 PUFA deprived (2% of total fatty acids) or an n-6 PUFA adequate (23% of total fatty acids) diet from weaning to 12 weeks of age. Animals then underwent intracerebroventricular surgery, in which lipopolysaccharide (LPS) was injected into the left lateral ventricle of the brain. Hippocampi were collected at baseline and following LPS administration (1, 3, 7, and 14 days). A microarray (n = 3 per group) was used to identify candidate genes and results were validated by real-time PCR in a separate cohort of animals (n = 5–8 per group). Results Mice administered with LPS had significantly increased Gene Ontology categories associated with inflammation and immune responses. These effects were independent of changes in gene expression in any diet group. Results were validated for the effect of LPS treatment on astrocyte, cytokine, and chemokine markers, as well as some results of the diets on Ifrd2 and Mfsd2a expression. Conclusions LPS administration increases pro-inflammatory and lipid-metabolizing gene expression in the mouse hippocampus. An n-6 PUFA deprived diet modulated inflammatory gene expression by both increasing and decreasing inflammatory gene expression, without impairing the resolution of neuroinflammation following LPS administration.

Download Full-text

Effect of Free Fatty Acids on Inflammatory Gene Expression and Hydrogen Peroxide Production by Ex Vivo Blood Mononuclear Cells

Nutrients ◽

10.3390/nu12010146 ◽

2020 ◽

Vol 12 (1) ◽

pp. 146 ◽

Cited By ~ 1

Author(s):

Antoni Sureda ◽

Miquel Martorell ◽

Maria del Mar Bibiloni ◽

Cristina Bouzas ◽

Laura Gallardo-Alfaro ◽

...

Keyword(s):

Gene Expression ◽

Fatty Acids ◽

Free Fatty Acids ◽

Mononuclear Cells ◽

Ex Vivo ◽

H2o2 Production ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Blood Mononuclear Cells ◽

Docosahexaenoic Acids

The aim of this study was to assess free fatty acids’ (FAs) ex vivo anti-/proinflammatory capabilities and their influence on inflammatory gene expression and H2O2 production by human peripheral blood mononuclear cells (PBMCs). Anthropometric and clinical measurements were performed in 26 participants with metabolic syndrome. Isolated PBMCs were incubated ex vivo for 2 h with several free fatty acids—palmitic, oleic, α-linolenic, γ-linolenic, arachidonic and docosahexaenoic at 50 μM, and lipopolysaccharide (LPS) alone or in combination. H2O2 production and IL6, NFκB, TLR2, TNFα, and COX-2 gene expressions were determined. Palmitic, γ-linolenic, and arachidonic acids showed minor effects on inflammatory gene expression, whereas oleic, α-linolenic, and docosahexaenoic acids reduced proinflammatory gene expression in LPS-stimulated PBMCs. Arachidonic and α-linolenic acids treatment enhanced LPS-stimulated H2O2 production by PBMCs, while palmitic, oleic, γ-linolenic, and docosahexaenoic acids did not exert significant effects. Oleic, α-linolenic, and docosahexaenoic acids induced anti-inflammatory responses in PBMCs. Arachidonic and α-linolenic acids enhanced the oxidative status of LPS-stimulated PBMCs. In conclusion, PBMC ex vivo assays are useful to assess the anti-/proinflammatory and redox-modulatory effects of fatty acids or other food bioactive compounds.

Download Full-text

Abstract 312: Transcriptional and Posttranscriptional Circuitry in the Brain After Transient and Permanent Ischemia

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.312 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Fatiha Tabet ◽

Sandy Lee ◽

Luisa F Cuesta Torres ◽

Michael G Levin ◽

Grant R Drummond ◽

...

Keyword(s):

Gene Expression ◽

Validation Studies ◽

Regulatory Networks ◽

Functional Roles ◽

Sham Procedure ◽

Gene Regulatory ◽

Neurological Processes ◽

The Brain

Background: Stroke is a major neurovascular disease and a leading cause of mortality and long-term disability. Within cells of the brain, short non-encoding microRNAs (miRNAs) serve to modulate gene expression and likely contribute to most, neurological processes. However, miRNA changes in the brain tissue in response to stroke have not been reported. Aim: To investigate the functional roles of brain miRNAs and gene regulatory networks in stroke injury. Methods: Adult (8-12 weeks old) male C57Bl/6 mice underwent intraluminal filament-induced middle cerebral artery (MCA) occlusion. Permanent ischemia (ischemia no reperfusion, InoR; n=8) was achieved by occlusion for 24 h, and ischemia with reperfusion (IR; n=8) was completed after 30 min of MCA followed by 23.5 h of reperfusion. Sham-operated mice (n=8) were used as controls. Total RNA was isolated from mouse brains and gene arrays (Affymetrix) and miRNA arrays (TaqMan OpenArray microRNA) were performed. Validation studies were performed using RT-PCR and TaqMan Individual Assays. Results: Relative to the sham-operated mice, InoR significantly altered (p≤0.05; fold-change≥1.5) the levels of 471 genes (mRNA) in the brain. By contrast, IR resulted in only 114 significant changes in gene expression after 24 h. Brain miRNAs were also very sensitive to both ischemia and reperfusion. 28 miRNAs (11 down, 17 up) were significantly altered by InoR compared to the sham procedure. Likewise, 12 miRNAs (3 down, 9 up) were significantly altered with reperfusion compared to the sham procedure. Interestingly, we found 10 miRNAs to be significantly altered (5 up, 5 down) with ischemia (InoR/Sham), but were also significantly corrected towards normal Sham levels by 23.5 h reperfusion (IR/InoR). Validation studies confirmed that levels of multiple miRNAs were significantly altered with InoR. Reperfusion increased the levels of all these miRNAs. 48% (327/680) of the mRNAs that were altered were predicted targets of significantly altered miRNAs, and our results showed inverse directional changes. Conclusion: Results from our study show the role of miRNAs and post-transcriptional circuits in both adaptive and maladaptive responses to ischemic stroke and reperfusion.

Download Full-text