Brain lipid modifications induced by essential fatty acid deficiency in growing male and female rats
TL;DR: It was found that essential fatty acid deficiency initiated in rats prior to birth and continued for one year affects brain lipids to an extent which differs in the two sexes.
Abstract: —Essential fatty acid (EFA) deficiency initiated in rats prior to birth and continued for one year affects brain lipids to an extent which differs in the two sexes. It was found that:
(1) Brain weight and lipid content were decreased in deficient conditions, especially in males.
(2) Total phospholipids were present in lower concentrations, particularly in the deficient male brain, while the percentage of the major phospholipid classes-ethanolamine phosphoglyceride (EPG), choline phosphoglyceride (CPG) and serine phosphoglyceride (SPG) did not change.
(3) Brain EPG, CPG and SPG had distinctive fatty acid patterns differing greatly in polyunsaturation content. PE acids of control females had elevated monoenes and reduced saturates in comparison with control males. This sex difference was lost in the deficient animals.
(4) Polyunsaturated fatty acids of EPG, CPG and SPG were markedly changed in animals lacking dietary linoleic acid. Trienoic (C20 and C22) and docosapentaenoic acids were greatly increased, whereas arachidonic, docosatetraenoic and docosahexaenoic acids were much decreased.
(5) In spite of the changes in fatty acid composition each of the three phospholipid classes maintained its particular level of unsaturation during EFA deficiency.
(6) EPG aldehydes did not change appreciably in deficient conditions.
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917 citations
TL;DR: The period of discovery of new lipids in the nervous system appears to be over and all the major lipid components have been discovered and a great deal is now known about their structure and metabolism.
694 citations
TL;DR: Strong evidence is now showing that a profound n-3 PUFA experimental deficiency is able to alter several neurotransmission systems, at least the dopaminergic and serotonergic, and reinforces the hypothesis that strong links exist between the PUFA status, aspects of brain function such as neurotransmission processes and behavior.
Abstract: We proposed several years ago that the behavioral effects of n -3 PUFA deficiency observed in animal models might be mediated through the dopaminergic and serotonergic systems that are very involved in the modulation of attention, motivation and emotion. We evaluated this hypothesis in an extended series of experiments on rats chronically diet-deficient in α -linolenic acid, the precursor of long-chain n -3 PUFA, in which we studied several parameters of these neurotransmission systems. The present paper synthesizes the main data we obtained on interactions between n -3 PUFA status and neurotransmission in animal models. We demonstrated that several parameters of neurotransmission were affected, such as the vesicular pool of dopamine and serotonin, thus inducing several regulatory processes such as modification of cerebral receptors in specific brain areas. We also demonstrated that (i) a reversal diet with adequate n -6 and n -3 PUFA given during the lactating period to rats originating from α -linolenic acid-deficient dams was able to restore both the fatty acid composition of brain membranes and several parameters of the dopaminergic and serotonergic neurotransmission, and (ii) when given from weaning, this reversal diet allowed partial recovery of biochemical parameters, but no recovery of neurochemical factors. The occurrence of profound n -3 PUFA deficiency during the lactating period could therefore be an environmental insult leading to irreversible damage to specific brain functions. Strong evidence is now showing that a profound n -3 PUFA experimental deficiency is able to alter several neurotransmission systems, at least the dopaminergic and serotonergic. Whether these experimental findings can be transposed to human pathophysiology must be taken cautiously, but reinforces the hypothesis that strong links exist between the PUFA status, aspects of brain function such as neurotransmission processes and behavior.
409 citations
Cites background from "Brain lipid modifications induced b..."
...On a biochemical point of view, this deficiency was accompanied in several brain areas with a large (around 70%) decrease in the amount of membrane n-3 PUFA, especially docosahexaenoic acid, associated to a compensatory rise in the total amount of n-6 PUFA, especially docosapentaenoic acid, as often described [21–24]....
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TL;DR: Analysis of the gangliosides by thin-layer chromatography showed that there was no selective enrichment of any individual type in the plasma membranes in relation to total brain, extending the specific fatty acid compositions observed in grey matter and certain sub-fractions by other workers.
395 citations
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TL;DR: The method reported here has the advantage of improved separations by two-dimensionM TLC, direct aspiration of spots by suction, and phosphorus analysis without pr ior elution.
Abstract: Quantitative Analysis of Phospholipids by Thin-Layer Chromatographyand Phosphorus Analysis of Spots p ROCEDURES FOR ANALYSIS of phospholipid composition by thin-layer chromatography (TLC) and phospho~nts analysis have been reported from a number of laboratories. These procedures usually depend upon one-dimensional TLC and elution of spots before analysis. The method reported here has the advantage of improved separations by two-dimensionM TLC, direct aspiration of spots by suction, and phosphorus analysis without pr ior elution. Our procedure depends upon two-dimensional TLC with the solvent pairs 1) chloroform/ methanol/water 65/25/4 a~ld n-butanol/acetic acid/water 60/20/20; and 2) chloroform/ methanol/2S% aqueous ammonia 65/35/5 followed by chloroform/acetone/methanol/acetic acid/water 5/271/1/0.5. The adsorbent composed of silica gel plain/magnesium silicate 9/1 (1) after spreading with a conventional Desaga spreader (0.25 nnn layer) is heat activated for 20 rain at 120C, cooled for 30 rain, spotted, and ehromatograms developed in chambers lined with solvent-saturated paper (2). Spots are detected by spraying with a 0.6% solution of potassium dichromate in 55% (by wt) sulfuric acid followed by heating for 30 rain at 180C in a forced draf t oven or by exposure to iodine vapors. Af ter development, spots are circled and lettered for identification and several blank areas corresponding in size to the sample spots are marked off. A typical ehromatogram of each series is photographed (Polaroid camera) and the spots recovered by aspiration. Aspirat ion of the spots directly into 30 ml Xjeldahl digestion flasks is accomplished by fitting a rubber stopper with two plastic tubes removed from plastic wash bottles. One tube with a pointed end serves as the intake and the other tube for attachment to a water pump for suction. Adsorbent is prevented from passing out of the digestion flask during aspiration by adding 0.9 ml of 72% perehlorie acid (used subsequently for digestion) to the flask to act as a liquid t rap by moistening the lower bulb portion of the flask and by insertion of a 1 cm square of \"Kimwipe\" or similar light weight paper into the end of the suction tube to serve as a filter. After aspiration, the plastic tubes are tapped to remove any dry powder and the paper filter pushed with a wire plunger into the flask. Digestion of the flask contents is carried out on an electrically heated Kjeldahl rack with water-pump suction to remove any escaping fumes. The heaters are adjusted to give gentle refluxing so that digestion is complete in about 20 rain. After digestion, the sides of the flask are rinsed with 5 ml of distilled water, 1 ml of 2.5% ammonium molybdate solution is added, the flask swirled for mixing, 1 ml of 10% ascorbic acid solution is added, and finally 2 nfl of distilled water are added. The solution is transferred to a centrifuge tube~ heated in a boiling water bath for 5 rain, cooled, and suspended adsorbent removed by eentrifugation for 5-10 rain. Samples and blanks are transferred to euvettes and the optical density determined at 820 m/x af ter zero adjustment with water. Sensitivity can be increased by using a 10 nfl digestion flask and one half of the specified amounts of reagents. Glassware should be acid eleaned. Corrected optical densities are determined by subtraction of the reading obtained from a blank area corresponding in size to that of the sample. The values are then converted to tLg of phosphorus using a factor derived from a standard curve prepared using Na~HPO~. The factor in our laboratories is 11.0 for standard amounts and twice that for half amounts of reagents. Molar ratios of phospholipids are obtained by expression of results as percent of the total phosphorus in the sample. Deterruination of the total phosphorus is conveniently accomplished by spotting 50-100 t~g of total sample in a blank area (upper right corner) after development with both solvents. The total sample is then charred, etc., in the same manner as the samples. For expression of results as percent of the total lipid, phosphorus values for brain lipids are multiplied by the following' factors: phosphatidyl bmsitol, 31.4; phosphatidyl serine, 26.2; lecithin and phosphatidyl ethanolamine, 25.4 ; phosphatidic acid, 25.0; sphingomyelin, 24.8; and cardiolipin, 24.4 Aninml tissue lipid extracts are spotted at levels of 200-1000 ~g for determinations and at least four ehromatograms are developed with each of the two-dimensional systems. Average values for the major lipid classes (lecithin, sphingomyelin, phosphatidyl ethanolamine and phosphatidyl serine) are thus obtained from eight determinations. Usually spots from two eh roma tog ra ms are pooled for minor components. The values obtained from a normal adult human brain by the present procedure and the
1,513 citations
TL;DR: In this article, the major lipids, including ethanolamine glycerophosphatides (EGP), serine glycephosphatide (SGP), choline glycephalophosphate (CGP), sphingomyelin, cerebroside, cerebrasides, and ceramide, were isolated from the frontal lobes of humans aged 10 months, 6 years, 9 years, and 55 years.
448 citations
TL;DR: In this paper, a rat was fed various levels of either linoleate, arachidonate, or ethyl linolenate, and the liver lipids were determined.
443 citations
TL;DR: After passage through the dextran gel columns, lipids eluted from thin-layer chromatograms were found to give infrared spectra identical to those of pure samples obtained by other procedures.
Abstract: A column chromatographic procedure is reported utilizing a dextran gel (Sephadex) for the complete separation of the major lipid classes from water-soluble nonlipids. Lipids other than gangliosides are eluted first with chloroform/methanol 19/1 saturated with water, gangliosides with chloroform/methanol/water containing acetic acid, and water-soluble nonlipids with methanol/water 1/1. Results for adult human whole brain, grey and white matter, and normal infant whole brain lipids are presented. With beef brain lipid as sample the ganglioside fraction is essentially pure, but with human brain lipid samples only about 70% of the second fraction is ganglioside. All ganglioside and water soluble nonlipid of a human spleen chloroform/methanol extract was separated from lipids with the procedure. Control studies with P32O4≡ and C14 labelled glucose showed that all counts were present in fraction 3. Similar studies with C14 labelled amino acids (glycine, serine, alanine, phenylalanine) showed that only phenylalanine counts were eluted in fraction 2 along with the gangliosides. The procedure was applied for removal of large amounts of ammonium acetate from DEAE cellulose column fractions and for complete removal of adsorbent and salts from lipids eluted from thin-layer chromatograms. After passage through the dextran gel columns, lipids eluted from thin-layer chromatograms were found to give infrared spectra identical to those of pure samples obtained by other procedures.
416 citations