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2021, Nature Communications
Polyunsaturated free fatty acids (FFAs) such as arachidonic acid, released by phospholipase activity on membrane phospholipids, have long been considered beneficial for learning and memory and are known modulators of neurotransmission and synaptic plasticity. However, the precise nature of other FFA and phospholipid changes in specific areas of the brain during learning is unknown. Here, using a targeted lipidomics approach to characterise FFAs and phospholipids across the rat brain, we demonstrated that the highest concentrations of these analytes were found in areas of the brain classically involved in fear learning and memory, such as the amygdala. Auditory fear conditioning led to an increase in saturated (particularly myristic and palmitic acids) and to a lesser extent unsaturated FFAs (predominantly arachidonic acid) in the amygdala and prefrontal cortex. Both fear conditioning and changes in FFA required activation of NMDA receptors. These results suggest a role for saturated FFAs in memory acquisition.
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2001
The aim of this work was to study the composition of long chain fatty acids and the n-6 and n-3 fattyacid ratios in aged and young Wistar rats in brain and hippocampus, related to relative cognitive deficits.The aged animals showed cognitive deficits during acquisition of a memory task (delayed alternation). In brain, results showed a decrease in palmitoleic and palmitic acid percentages in all the studied phospholipid classes and in the phosphatidylserine and phosphatidylcholine classes, respectively, in old rats, compared to the young ones.There was also an increase in oleic and stearic acid amounts in the sphingomyelin, phosphatidylserine and phosphatidylinositol classes and in the phosphatidylserine and phosphatidylcholine classes, respectively. Arachidonic acid amount was decreased in old rats, compared to the young ones, in the phosphatidylserine and phosphatidylinositol classes.Totaln-6 and n-3 fattyacid amounts were both decreased in all phospholipid classes, with a stable n-6/n-3 ratio. Our results confirm that arachidonic acid concentration is decreased in aged rats and that this reduction, more significant in phosphatidylserine and phosphatidylinositol classes, should be related to the fact that low concentrations of arachidonic acid are observed during activation of glutamate receptor.
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 1998
Abbreviations: cerebellum (CB), frontal cortex (FC), hippocampus (HC), hypothalamus (HT), occipital cortex (OC), pituitary (PIT), striatum (ST). Rats fed rat chow with: 6% soybean oil = normal standard (group C), 6% primrose oil (group P), 6 % fish oil (group F), a combination of 4.5% primrose and 1.5% fish oil (group P+ F).
The Journal of Lipid Research
In this study, we have examined the effects of n-3 fatty acid deficient diets on the phospholipids (PL) molecular species composition in the hippocampus. Female rats were raised for two generations on diets containing linoleic acid (18:2n-6), with or without supplementation of alpha-linolenic acid (18:3n-3) or 18:3n-3 plus docosahexaenoic acid (22:6n-3). At 84 days of age, the hippocampal phospholipids were analyzed by reversed phase HPLC-electrospray ionization mass spectrometry. Depleting n-3 fatty acids from the diet led to a reduction of 22:6n-3 molecular species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), PE-plasmalogens (PLE), and phosphatidylserine (PS) by 70-80%. In general, 22:6n-3 was replaced with 22:5n-6 but the replacement at the molecular species level did not always occur in a reciprocal manner, especially in PC and PLE. In PC, the 16:0,22:6n-3 species was replaced by 16:0,22:5n-6 and 18:0,22:5n-6. In PLE, substantial increases of both 22:5n-6 and 22:4...
Journal of …, 2008
Using an in vivo fatty acid model and operational equations, we reported that esteri®ed and unesteri®ed concentrations of docosahexaenoic acid (DHA, 22 : 6 n-3) were markedly reduced in brains of third-generation (F3) rats nutritionally deprived of a-linolenic acid (18 : 3 n-3), and that DHA turnover within phospholipids was reduced as well. The concentration of docosapentaenoic acid (DPA, 22 : 5 n-6), an arachidonic acid (AA, 20 : 4 n-6) elongation/desaturation product, was barely detectable in control rats but was elevated in the deprived rats. In the present study, we used the same in vivo model, involving the intravenous infusion of radiolabeled AA to demonstrate that concentrations of unesteri®ed and esteri®ed AA, and turnover of AA within phospholipids, were not altered in brains of awake F3-generation n-3-de®cient rats, compared with control concentrations. Brain DPA-CoA could be measured in the deprived but not control rats, and AA-CoA was elevated in the deprived animals. These results indicated that AA and DHA are recycled within brain phospholipids independently of each other, suggesting that recycling is regulated independently by AA-and DHAselective enzymes, respectively. Competition among n-3 and n-6 fatty acids within brain probably does not occur at the level of recycling, but at levels of elongation and desaturation (hence greater production of DPA during n-3 deprivation), or conversion to bioactive eicosanoids and other metabolites.
Journal of Lipid Research, 2009
cursors, ␣-linolenic acid (ALA; 18:3n-3) and linoleic acid (LA; 18:2n-6), respectively (4-8). The rate of brain desaturation and elongation of plasma unesterifi ed ALA and LA into DHA and AA, respectively, has been shown to be <1% of the brain rate of uptake of preformed DHA and AA from plasma in vivo (7, 9). One area of interest in these PUFAs is with regards to brain development and function, as the brain is highly enriched in both DHA and AA (10). Currently, DHA is being investigated for its potential neuroprotective and anti-infl ammatory properties (11-13). Alternatively, understanding AA-mediated signal transduction and metabolism within the brain may provide insight into a variety of neurological and neurodegenerative disorders. Several studies have shown that widely used mood stabilizers target turnover and enzymatic pathways of AA (14, 15). Other studies have implicated upregulated AA signaling cascades in Alzheimer's disease and vascular dementia (16), Multiple Sclerosis (17), and Parkinson's disease (18, 19). AA entry into the brain may originate from several sources, including the plasma unesterifi ed pool, or via lipoproteins, including HDL, LDL, and VLDL; lipoprotein receptors have been identifi ed on the blood brain barrier (20). Chen et al. (21) examined the contribution of the LDL pathway of PUFA entry into the brain by comparing brain phospholipid PUFA levels in LDL-knockout and wild-type mice and found no signifi cant difference. However, it is unknown whether other pathways of entry (HDL, VLDL, unesterifi ed, lysophosphatidylcholine, etc.) compensated for the lack of infl ux from the LDL pool. Contreras et al. (22) infused unesterifi ed radiolabeled AA into the femoral vein of awake third-generation n-3 PUFA deprived rats and calculated the rate of unesterifi ed AA entry Abstract Previous studies have infused radiolabeled arachidonic acid (AA) into rat brains and followed AA esterifi cation into phospholipids for up to 24 h; however, the half-life of AA in rat brain phospholipids is unknown. Eighteen day old rats were fed either an n-3 PUFA adequate or deprived diet for 15 weeks. Following the 15 weeks, 40 µCi of [ 3 H] AA was injected intracerebroventricularly into the right lateral ventricle using stereotaxic surgery and returned to their dietary treatment. From 4-120 days after [ 3 H] AA administration, brains were collected for chemical analyses. The half-life of AA in rat brain phospholipids was 44 ± 4 days for the n-3 PUFA adequate group and 46 ± 4 days for the n-3 PUFA deprived group, which closely approximates the predicted half-life previously reported, based on the rate of entry from the plasma unesterifi ed pool, suggesting the plasma unesterifi ed pool is a major contributor to brain uptake of AA. Furthermore, unlike a previous report in which the half-life of brain phospholipid docosahexaenoic acid (DHA) was increased in n-3 PUFA deprived rats, n-3 PUFA deprivation did not signifi cantly alter the AA half-life, suggesting different mechanisms exist to maintain brain concentrations of AA and DHA.-Green, J. T., Z. Liu, and R. P. Bazinet. Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived diet.
Neuroscience, 2011
Here we evaluated the influence of physical exercise on behavior parameters and enzymatic status of rats supplemented with different dietary fatty acids (FA). Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30 min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety-like symptoms in the animals, but after physical exercise, SO group showed a better behavioral performance than L and the HVF groups in elevated plus maze (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared to L group, and exercise reversed this effect. SO-fed rats showed an improvement in memory acquisition after 1 day of training, whereas lard caused an improvement of memory only from day 4. HVF-fed rats showed no improvement of memory acquisition, but this effect was reversed by exercise in all training days. A lower activity of the Na ؉ K ؉ -ATPase in brain cortex of rats fed lard and HVF was observed, and this effect was maintained after exercise. Similarly, the HVF diet was related to lower activity of hippocampal Na ؉ K ؉ -ATPase, and exercise reduced activity of this enzyme in the SO and L groups. Our findings show influences of dietary FA on memory acquisition, whereas regular exercise improved this function and was beneficial on anxiety-like symptoms. As FA are present in neuronal membrane phospholipids and play a critical role in brain function, our results suggest that low incorporation of trans FA in neuronal membranes may act on cortical and hippocampal Na ؉ K ؉ -ATPase activity, but this change appears to be unrelated to the behavioral parameters primarily harmed by consumption of trans and less so by saturated FA, which were reversed by exercise.
Reproduction Nutrition Development, 2005
This issue of Reproduction Nutrition Development was scheduled along with 8 papers on the metabolism of polyunsaturated fatty acids (PUFAs) and their physiological roles within the central nervous system. Topics focused on PUFAs from the n-3 series, especially on docosahexaenoic acid (DHA) which is particularly abundant in the cell membranes of brain and retina. Reviews and original articles emphasize the impact of n-3 PUFAs on the physical properties of membranes, the neuroprotective mechanisms via Ca 2+ signalling in astrocytes, the n-3 status of infants suffering of Attention Deficit Hyperactivity Disorder (ADHD) and the mental development of neonates in relation with maternal feeding. The DHA metabolism in humans and its endogenous production from alpha-linolenic acid is reviewed. Besides, it is described and discussed how the generation of PUFAderived mediators is modulated by the retinoic acid-receptor signalling via activation of cognate phospholipase activities. The sensitivity and recovering of neurons to oxidative stress is also addressed in this volume, through the description of a model of iron-induced injury in the rat brain. The diversity of these 8 articles illustrates the multiple roles of PUFAs within the central nervous system. arachidonic acid / astrocytes and calcium signalling / Attention Deficit Hyperactivity Disorder / central nervous sytem / docosahexaenoic acid / endogenous conversion / membrane physical properties / milk and infant mental development / omega-3 and omega-6 fatty acids / oxidative stress / phospholipases / raft / retinoic acid * Corresponding author: [email protected]
Peptides, 1998
YEHUDA, S., S. RABINOVITZ., R. L. CARASSO AND D. I. MOSTOFSKY. Fatty acids and brain peptides. PEPTIDES 19(2) 407-419, 1998.-The role of fatty acids (FA) as a mediator and modulator of central nervous system activity in general, and peptides in particular, is only recently becoming understood. This paper reviews numerous findings concerned with the activity of fatty acids, particularly with their interaction with diverse neurochemical systems and their consequences for better understanding neurotransmitters, hormones and peptides. The effects include FA as precursors in the manufacture of neurochemical elements, including enzymes, neurotransmitters, and hormones. Of particular interest is the important changes in neuronal membrane composition that have been attributed to FA. Such changes may account for the changes in thermoregulation, learning, and other functions that accompany dietary manipulation of FA intake. While the total level of FA has been the object of many investigations, this report addresses the need to focus on the ratio of FA, especially ␣-linolenic/ linoleic acid, which has been shown to be a critical factor in a number of research studies.
Lipids, 1996
Release of specific polyunsaturated fatty acids from cell membranes may have a significant implication in biological function, considering the involvement of various fatty acids in cell signal transduction. In the present study, release of polyunsaturated fatty acids from rat brain synaptosomes by endogenous synaptosomal lipase activity was examined in comparison to that by cobra venom phospholipase A 2 (Naja naja naja). Cobra venom phospholipase A 2 (Naja naja naja) preferentially hydrolyzed docosahexaenoic acid (22:6n-3) from both synaptosomes and lipid mixtures containing similar classes of lipids commonly found in the brain. Arachidonic acid (20:4n-6) and oleic acid (18:1n-9) were also hydrolyzed; however, monoene species was hydrolyzed slower than were polyenoic species in synaptosomes. Phosphatidylethanolamine was the most preferred phospholipid class for release of 22:6n-3 fatty acid from both lipid mixtures and synaptosomes.
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 ...
Prostaglandins, Leukotrienes and Essential Fatty Acids, 2008
The brain is particularly enriched in glycerophospholipids with either arachidonic or docosahexaenoic acid esterified in the stereospecifically numbered-2 position. In this paper, we review how combining a kinetic approach to study the uptake and turnover of arachidonic and docosahexaenoic acids within brain phospholipids of unanesthetized rats, along with chronic administration of antimanic drugs (lithium, valproate and carbamazepine), have advanced our understanding of how polyunsaturated fatty acids (PUFA) enter the brain, and the mechanisms that regulate their turnover within brain phospholipids. The incorporation rates of arachidonic and docosahexaenoic acid from the plasma unesterified pool into brain phospholipids closely approximate independent measures of their consumption rates by the brain, suggesting this is quantitatively the major pool for uptake of these PUFA. Antimanic drugs (lithium and carbamazepine) that downregulate the activity of the calciumdependent cytosolic phospholipase A 2 (cPLA 2) transcription factor AP-2, and in turn the expression and activity of cPLA 2, lead to a selective downregulation in brain arachidonic acid turnover. Furthermore, targeting arachidonoyl-CoA formation via ordered, non-competitive inhibition of an acyl-CoA synthetase with valproate also selectively decreases brain arachidonic acid turnover. Drugs that increase brain cPLA 2 activity (N-methyl-D-aspartic acid and fluoxetine) are correlated with increased turnover of arachidonic acid in brain phospholipids. Altered PUFA metabolism has been implicated in several neurological disorders, including bipolar disorder and Alzheimer's disease. Identifying the enzymes that regulated brain PUFA metabolism could lead to new therapeutic approaches for these disorders.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2003
Rats were fed from conception till adulthood either with normal rat chow with a linoleic (LA) to linolenic acid (LNA) ratio of 8.2:1 or a rat chow supplemented with a mixture of perilla and soy bean oil giving a ratio of LA to LNA of 4.7:1. Fat content of the feed was 5%. Fatty acid and molecular species composition of ethanolamine phosphoglyceride was determined. Effect of this diet on gene expression was also studied. There was an accumulation of docosahexaenoic (DHA) and arachidonic acids (AA) in brains of the experimental animals. Changes in the ratio sn-1 saturated, sn-2 docosahexaenoic to sn-1 monounsaturated, sn-2 docosahexaenoic were observed. Twenty genes were found overexpressed in response to the 4.7:1 mixture diet and four were found down-regulated compared to normal rat chow. Among them were the genes related to energy household, lipid metabolism and respiration. The degree of up-regulation exceeded that observed with perilla with a ratio of LA to LNA 8.2:1 [Proc. Natl. Acad. Sci. U. S. A. 99 ]. It was concluded that brain sensitively reacts to the fatty acid composition of the diet. It was suggested that alteration in membrane architecture and function coupled with alterations in gene expression profiles may contribute to the observed beneficial impact of n À 3 type polyunsaturated fatty acids on cognitive functions. D
The Journal of Lipid Research, 2007
Whereas antibipolar drug administration to rats reduces brain arachidonic acid turnover, excessive Nmethyl-D-aspartate (NMDA) signaling is thought to contribute to bipolar disorder symptoms and may increase arachidonic acid turnover in rat brain phospholipids. To determine whether chronic NMDA would increase brain arachidonic acid turnover, rats were daily administered NMDA (25 mg/kg, ip) or vehicle for 21 days. In unanesthetized rats, on day 21, [1-14 C]arachidonic acid was infused intravenously and arterial blood plasma was sampled until the animal was euthanized at 5 min and its microwaved brain was subjected to chemical and radiotracer analysis. Using equations from our in vivo fatty acid model, we found that compared with controls, chronic NMDA increased the net rate of incorporation of plasma unesterified arachidonic acid into brain phospholipids (25-34%) as well as the turnover of arachidonic acid within brain phospholipids (35-58%). These changes were absent at 3 h after a single NMDA injection. The changes, opposite to those after chronic administration of antimanic drugs to rats, suggest that excessive NMDA signaling via arachidonic acid may be a model of upregulated arachidonic acid turnover in brain phospholipids.
Neurochemical Research, 1986
The effect of electroconvulsive shock on the labeling of phospholipids and neutral lipids in mice brains was examined after intracerebral injection of [1-14C] arachidonic acid or [1-14C]palmitic acid. Electroconvulsive shock reduced greatly the removal of radiolabeled arachidonic acid from the free fatty acid pool. At the same time, the incorporation of arachidonic acid was partially inhibited in triacylglycerol, diacylglycerol, and phosphatidylinositol, whereas the incorporation of [1-14C]palmitic acid was not affected. Pretreatment with desipramine and 218 PED1CONI pargyline potentiated the lipid effect of electroconvulsive shock in neutral glycerides. These electroconvulsive shock-induced changes reflect alterations in the metabolism of intracerebrally injected arachidonic acid, but not of similarly injected palmitic acid. From the available data whether decreased ATP, enzyme inhibition or other factors are involved cannot be ascertained. Moreover, the electroconvulsive shock-enhanced endogenous free arachidonic acid may possibly dilute the injected radiolabeled fatty acid, thus decreasing its availability for arachidonoyl-coenzyme A synthesis. Hence, a partial inhibition of the activationacylation of these fatty acids, primarily arachidonic acid, also may be involved in the seizure-induced accumulation of free fatty acids in the brain.
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
Nutrition (Burbank, Los Angeles County, Calif.), 2003
Neurochemistry International, 1997
Long-term potentiation (LTP), a model of activity-dependent synaptic plasticity and of certain forms of memory, comprises the persistent enhancement of excitatory neurotransmission that results from high-frequency activation. A presynaptic component of LTP is thought to be modulated by a retrograde messenger generated by the postsynaptic neuron. Arachidonic acid, nitric oxide, carbon monoxide and PAF have each been proposed as retrograde messengers in LTP, but arachidonic acid, unlike PAF, requires NMDA receptor activation. A PAF antagonist (BN 52021) that provides neuroprotection in ischemiareperfusion displaces [3H] PAF bound to presynaptic membranes, blocks PAF-induced glutamate exocytosis and inhibits LTP. An antagonist selective for the intracellular PAF binding site (BN 50730) did not affect LTP, nor did BN 52021 modify NMDA currents. LTP was induced with weak synaptic stimulation coupled with postsynaptically administered enzyme resistant rncPAF. Theta-burst stimulation (10 min) after bath applications of mcPAF (1 #M) induced APV-independent LTP that was blocked by 5 /~M BN 52021. When this antagonist was infused into the hippocampus before or immediately after training, it impaired memory of inhibitory avoidance training in the rat. Memory was not altered if the antagonist is infused 30 or 60 min after training. Moreover, mcPAF enhances memoTy on retention test performance of step-down inhibitory avoidance habituation and learning in rats. Also, memory was studied using a caudate nucleus-dependent cued water maze task. Rats received an 8 trial (30 s intertrial interval) training session in which a visible cued escape platform was located in a different quadrant of the maze of each trial. Following trial 8, the rats received a unilateral post-training intra-caudate injection of mcPAF (1 /~g/0.5/A), BN 52021 (0.5/~g/0.5 #1) or vehicle. On a retention test session 24 h later, latency to mount the escape platform was used as a measure of memory. The retention test escape latencies of rats given mcPAF were significantly lower than those of the vehicle-injected controls, indicating a memory enhancing effect of mcPAF. Injection of mcPAF did not affect retention when administered 2 h post-training, indicating a time-dependent effect of mcPAF on memory. The latencies for animals injected with BN 52021 were significantly higher than those of the controls, indicating that antagonism of endogenous PAF impairs memory. The findings show that PAF plays a role in memory formation in a caudate-mediated cued discrimination task. Administration of BN 52021 2 h post-training had no affect on retention, indicating a time-dependent effect of endogenous PAF on memory formation. PAF, the most potent bioactive lipid known, modulates excitatory synaptic transmission, neuronal plasticity and memory. When PAF production is overstimulated as in seizures or ischemia, it becomes neurotoxic. Copyright ~_:) 1996 Elsevier Science Ltd Excitatory amino acids (EAA) are neurotransmitters which mediate important physiological and pathophysiological events in the CNS. Under physiological conditions, they are involved in defined pathways of neurotransmission, synaptic plasticity, and information processing (for recent reviews see Miller et al.,
Medical Hypotheses, 2012
Polyunsaturated essential fatty acids (PUFAs) play a pivotal role in mediating cognitive, learning, and memory functions. We propose that PUFAs directly affect the neuronal membrane. PUFAs serve to stabilize and protect the structure and functions of the neuronal membrane. PUFAs exert many effects on the brain with respect to physiology, brain biochemistry, and disorders of the central nervous system. Many of these functions have effects at the cognitive level. This summary demonstrates that a deficiency in brain PUFAs will lead to cognitive deficits, while supplementation of PUFAs can rehabilitate cognitive deficits, as manifested in attention deficit hyperactivity disorder, stress/anxiety, and aging.
Neuroscience Letters, 1994
The incorporation of [3H]arachidonic acid (20:4n-6) into rat brain membranes and its mobilization in response to norepinephrine, a relevant neuromediator were studied. The most efficient [3H]20:4n-6 incorporation was in inositol glycerophospholipids (PI) where it reached a plateau after 10 min incubation, while this incorporation was very weak in choline glycerophospholipids (PC). In contrast, the esterification of docosahexaenoic acid, another polyunsaturated fatty acid occurring at high level in brain, was similar in PI and PC, the incorporation in PI being 8-fold lower than that of 20:4n-6. The newly esterified [3H]20:4n-6 was exclusively found in the 1.2-diacyl subclasses of Pl and PC. The bulk of incorporation was in the 18:0/20:4n-6 molecular species of 1,2-diacyl-glycerophosphoinositol and in 16:0/20:4n-6 + 18:1/20:4n-6 molecular species of 1,2-diacyl-glycerophosphocholine, which agrees with the usual location of 20:4n-6 in brain phospholipid classes. Upon norepinephrine treatment, [3H]20:4n-6 was not released from PC, but was dose-dependently decreased in PI, the release being significant from 10 5 M of the agonist. These results suggest that 20:4n-6 exhibits a high specific turnover in brain PI and is mobilized from this class upon relevant neuromediator stimulation. The acellular system used preserved the specificity of enzymes catalyzing the polyunsaturated fatty acid incorporation and release and could be helpful for studying their turn over in brain.
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