Multiple facets of membrane lipids and the diversity of their action mode with special emphasis on the central nervous system (original) (raw)
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Reproduction, nutrition, development
Docosahexaenoic acid (DHA, 22:6n-3) and arachidonic acid (AA, 20:4n-6) are the major polyunsaturated fatty acids in the membranes of brain and retinal cells. Animals specifically deficient in dietary n-3 fatty acids have low DHA content in their membranes, reduced visual acuity and impaired learning ability. Studies on bottle-fed human infants have shown that adding DHA and AA to milk replacer-formulas can bring their concentrations in the infant blood lipids to values as high as those produced by breast-feeding and significantly improves mental development and maturation of visual function. In older subjects, diverse neuropsychiatric and neurodegenerative diseases have been associated to decreased blood levels of n-3 PUFA. Low intakes of fish or of n-3 PUFA in populations have been associated with increased risks of depression and Alzheimer disease, and n-3 PUFA, especially eicosapentaenoic acid (EPA, 20:5n-3), have shown efficacy as adjunctive treatment - and in some cases as the ...
Pediatric Research, 2005
N-3 fatty acid deficiency has been related to decreased docosahexaenoic acid (DHA) and increased docosapentaenoic acid (DPA) levels in brain and to learning disadvantages. The influence of n-3 deficiency and supplementation on brain fatty acids and learning were investigated in young rats. Newborn Wistar rats were assigned to three groups of cross-foster mothers. The control group (C) was nursed by mothers that received essential fatty acids during pregnancy and lactation, and the deficient group (D) was nursed by mothers that did not receive those fatty acids. The supplemental group (S) had the same conditions as D, receiving an additional DHA and arachidonic acid supplement during lactation. Cerebral cortex and hippocampus fatty acid composition was examined using thin-layer and capillary column gas chromatography, and learning was measured by passive-avoidance procedure. D brains showed low DHA and high DPA levels, but S brain composition was similar to C. Learning in the S group was unaffected, but in the D group, it was poorer than C. Learning was directly correlated with DHA levels and inversely with DPA levels in brain. Low DHA and high DPA brain levels both were correlated with poor learning. DPA seems not to be a suitable brain functional analogue of DHA, and DHA supplementation reversed both biochemical and learning adverse effects observed in n-3 deficiency. (Pediatr Res 57: 719-723, 2005) Abbreviations AA, arachidonic acid DHA, docosahexaenoic acid DPA, docosapentaenoic acid EFA, essential fatty acid FA, fatty acid IQR, interquartile range LCPUFA, long-chain polyunsaturated fatty acids PC, phosphatidylcholine PE, phosphatidylethanolamine PI, phosphatidylinositol PS, phosphatidylserine SFA, saturated fatty acids STL, step-through latency
Essential fatty acids and the brain: possible health implications
International Journal of Developmental Neuroscience, 2000
Linoleic and a-linolenic acid are essential for normal cellular function, and act as precursors for the synthesis of longer chained polyunsaturated fatty acids (PUFAs) such as arachidonic (AA), eicosapentaenoic (EPA) and docosahexaenoic acids (DHA), which have been shown to partake in numerous cellular functions aecting membrane¯uidity, membrane enzyme activities and eicosanoid synthesis. The brain is particularly rich in PUFAs such as DHA, and changes in tissue membrane composition of these PUFAs re¯ect that of the dietary source. The decline in structural and functional integrity of this tissue appears to correlate with loss in membrane DHA concentrations. Arachidonic acid, also predominant in this tissue, is a major precursor for the synthesis of eicosanoids, that serve as intracellular or extracellular signals. With aging comes a likely increase in reactive oxygen species and hence a concomitant decline in membrane PUFA concentrations, and with it, cognitive impairment. Neurodegenerative disorders such as Parkinson's and Alzheimer's disease also appear to exhibit membrane loss of PUFAs. Thus it may be that an optimal diet with a balance of n-6 and n-3 fatty acids may help to delay their onset or reduce the insult to brain functions which these diseases elicit. Published by
Role of essential fatty acids in the function of the developing nervous system
Lipids, 1996
The basis for n-3 fatty acid essentiality in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by α-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.
Docosahexaenoic and Arachidonic Acids as Neuroprotective Nutrients throughout the Life Cycle
Nutrients
The role of docosahexaenoic acid (DHA) and arachidonic acid (AA) in neurogenesis and brain development throughout the life cycle is fundamental. DHA and AA are long-chain polyunsaturated fatty acids (LCPUFA) vital for many human physiological processes, such as signaling pathways, gene expression, structure and function of membranes, among others. DHA and AA are deposited into the lipids of cell membranes that form the gray matter representing approximately 25% of the total content of brain fatty acids. Both fatty acids have effects on neuronal growth and differentiation through the modulation of the physical properties of neuronal membranes, signal transduction associated with G proteins, and gene expression. DHA and AA have a relevant role in neuroprotection against neurodegenerative pathologies such as Alzheimer’s disease and Parkinson’s disease, which are associated with characteristic pathological expressions as mitochondrial dysfunction, neuroinflammation, and oxidative stress...
Does Maternal Arachidonic Acid Influence the Neurodevelopmental Effects of Docosahexaenoic Acid?
2021
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.
Journal of Lipid Research, 1999
Information on the prenatal accumulation of rat brain membrane lipids is scarce. In this study we investigated in detail the fatty acid (FA) composition of the rat brain, on each day from embryonic day 12 (E12) up to birth, and on 8 time points during the first 16 days of postnatal life, and correlated the FA changes with welldescribed events of neurogenesis and synaptogenesis. Between E14 and E17, there was a steep increase in the concentration of all the FAs: 16:0 increased by 136%, 18:0 by 139%, 18:1 by 92%, 20:4n-6 by 98%, 22:4n-6 by 116%, 22:5n-6 by 220%, and 22:6n-3 by 98%. After this period and up to birth, the concentration of the FAs plateaued, except that of 22:6n-3, which accumulated further, reaching an additional increase of 75%. After birth, except 22:5n-6, all FAs steadily increased at various rates. Estimation of the FA/PL molar ratios showed that prenatally the ratios of all the FAs either decreased or remained constant, but that of 22:6n-3 increased more than 2-fold; postnatally the ratios remained constant, with the exception of 22:4n-6 and 22:5n-6, which decreased. In conclusion, prenatal accumulation of brain fatty acids parallels important events in neurogenesis. 22:6n-3 is exceptional inasmuch in its steep accumulation occurs just prior to synaptogenesis.-Green, P., S. Glozman, B. Kamensky, and E. Yavin. Developmental chantes in rat brain membrane lipids and fatty acids: the preferential prenatal accumulation of docosahexaenoic acid.
Brain Research, 2008
Docosahexaenoic acid (DHA, 22:6ω-3) is a major polyunsaturated fatty acid in the brain and is required in large amounts during development. Low levels of DHA in the brain are associated with functional deficits. The ω-3 fatty acids are essential nutrients and their metabolism and incorporation in developing brain depends on the composition of dietary fat. We assessed the importance of the intake of the ω-3 fatty acid, 18:3ω-3 and the balance with the ω-6 fatty acid, 18:2ω-6, and the effects of dietary arachidonic acid (20:4ω-6) and DHA in milk diets using the piglet as a model of early infant nutrition. Piglets were fed (% energy) 1.2% 18:2ω-6 and 0.05% 18:3ω-3 (deficient), 10.7% 18:2ω-6 and 1.1% 18:3ω-3 (contemporary), 1.2% 18:2ω-6 and 1.1% 18:3ω-3 (evolutionary), or the contemporary diet with 0.3% 20:4ω-6 and 0.3% DHA (supplemented) from birth to 30 days of age. Our results show that a contemporary diet, high in 18:2ω-6 compromises DHA accretion and leads to increased 22:4ω-6 and 22:5ω-6 in the brain. However, an evolutionary diet, low in 18:2ω-6, supports high brain DHA. DHA supplementation effectively increased DHA, but not the intermediate ω-3 fatty acids, 20:5ω-3 and 22:5ω-3. Using primary cultures of cortical neurons, we show that 22:5ω-6 is efficiently acylated and preferentially taken up over DHA. However, DHA, but not 22:5ω-6 supports growth of secondary neurites. Our results suggest the need to consider whether current high dietary ω-6 fatty acid intakes compromise brain DHA accretion and contribute to poor neurodevelopment.
Nutrients, 2021
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 devel...
Nutrition & Metabolism, 2010
Background: Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates. Methods: Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics. Results: In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA. Conclusion: The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.