Why is docosahexaenoic acid essential for nervous system function?
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Animals↗
Biomedical subjects
N Salem
Publications and source records attributed to N Salem.
Study of subcellular localization of membrane-bound choline acetyltransferase in Drosophila central nervous system and its association with membranes.
Choline acetyltransferase (ChAT), the enzyme which catalyses the biosynthesis of the neurotransmitter acetylcholine, exists in a soluble and membrane-bound form in cholinergic nerve terminals of different animal species. This study was performed on the enzyme present in Drosophila central nervous system. We show that the two forms of the enzyme have the same apparent molecular weight (75 kDa) when analysed by immunoblotting using an antibody we raised against the recombinant enzyme. According to different authors, membrane-bound enzyme might be associated with synaptic vesicles or plasma membrane. Subfractionation of Drosophila head homogenates in linear glycerol gradients showed that ChAT does not associate with synaptic vesicles. Analysis of ChAT activity and immunoreactivity showed that two peaks of ChAT were produced. One peak was present in fractions containing soluble components and the other was associated with rapidly sedimenting membranes containing plasma membranes. ChAT in the first peak was mainly hydrophilic. A large proportion of ChAT associated with rapidly sedimenting membranes was amphiphilic. Further fractionation of these membranes by flotation in sucrose gradients showed that membrane-associated ChAT sedimented in fractions containing plasma membrane marker. Membrane-bound ChAT was neither solubilized nor converted to hydrophilic enzyme after membrane treatment with 1 M hydroxylamine, suggesting that the enzyme is not palmitoylated and therefore not anchored to membrane through thioester-linked long chain fatty acid. Partial solubilization of ChAT present on membranes with urea and carbonate suggests that this form of ChAT is a peripheral membrane protein. Carbonate solubilization of membrane-bound ChAT converted the enzyme from hydrophobic to hydrophilic protein.
Alkalies↗
Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain in microsomes and C6 glioma cells.
Docosahexaenoic acid (22:6n-3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n-3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n-3-deficient diet showed a dramatic reduction of 22:6n-3 content (1.7 +/- 0.1%) when compared with control animals (15.0 +/- 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n-6) content, which replaced the 22:6n-3 phospholipids with 22:5n-6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n-3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1-stearoyl-2-docosapentanoyl (18:0/22:5n-6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n-3-deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n-3-supplemented media (10-40 microM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n-3 may be a modulator of PS synthesis.
Animals↗
Detecting measurement confounding in epidemiological research: construct validity in scaling risk behaviours: based on a population sample in Minnesota, USA.
STUDY OBJECTIVE: The purpose of this study was to construct and validate a behavioral risk index scale to determine if the scaled variable could be used to study possible latent dimensions of risk behaviour. DESIGN: Data from the Minnesota Behavioral Risk Factor Surveillance System (BRFSS) were used to construct and validate a behavioral risk index using item response theory methods. PARTICIPANTS: A representative sample of 3303 Minnesota adults 18 years of age and older. RESULTS: Massive evidence was found against the construct validity of the index scale as a measure of risk behaviour. Seven commonly studied risk behaviours could not be scaled into a valid construct of health behaviour for either men or women. Tests of scalability, homogeneity, and item independence were rejected. In addition, item bias was found for all of the items in relation to important exogenous variables, especially age and education. CONCLUSIONS: The risk behaviours do not represent sufficiently similar types of phenomena to form an additive scale of health related risk taking. Not only do the practices fall on different, undefined dimensions of behavior, subgroup differences in risk taking would be hidden by data reductions summing the behavioral practices into additive scales. The findings indicate that the behaviors have quite distinct meanings that should be studied separately.
Adolescent↗
Long-chain polyunsaturated fatty acids.
Long-chain polyunsaturated fatty acids (LC-PUFA) are essential for normal development. Fetal accretion of LC-PUFA occurs during the last trimester of gestation; therefore, premature infants are born with minimal LC-PUFA reserves. Recent studies indicate that the newborn can synthesize LC-PUFA from essential fatty acid precursors; however, the extent of de novo synthesis remains to be established. Postnatally, human milk provides LC-PUFA to the newborn. Maternal LC-PUFA reserves depend upon diet and can be improved by supplementation of docosahexaenoic acid and arachidonic acid during pregnancy and lactation. This in turn affects fetal LC-PUFA accretion and postnatal provision through mother's milk. Supplementation of formula-fed preterm or full-term infants with docosahexaenoic acid and arachidonic acid leads to plasma and red blood cell LC-PUFA levels similar to those of breast-fed infants. The higher blood and presumably tissue levels of LC-PUFA following supplementation lead, however, to only temporary functional benefits.
Animals↗
[Complete remission of a mesenteric fibromatosis after taking sulindac].
We report the case of a 22-year-old-man having a familial adenomatous polyposis coli treated by total colectomy with ileo-rectal anastomosis. Two years after the operation, an asymptomatic mesenteric fibromatosis appeared which was nonresectable due to mesenteric vessels infiltration. Nine years later, sulindac therapy was started for residual polyps in the rectal stump. This treatment was taken intermittently, during periods of 1 to 8 months, for 6 years. After 4 years of treatment, the tumor was no longer palpable. Four years after sulindac discontinuation, the patient was operated on for suspicion of intestinal adhesion. The mesenteric fibromatosis had completely disappeared and mesenteric vessels were free. This complete macroscopic regression of a desmoid tumor after sulindac therapy emphasizes again the interest of this treatment for mesenteric fibromatosis.
Adenomatous Polyposis Coli↗
N-3 fatty acid deficiency in the rat pineal gland: effects on phospholipid molecular species composition and endogenous levels of melatonin and lipoxygenase products.
N-3 essential fatty acid deficiency affects a number of biological and physiological processes. In this study, we investigated the effect of n-3 essential fatty acid status on two key pineal biochemical functions, melatonin production and lipoxygenation, using pineal glands from rats given an n-3-adequate or n-3-deficient diet. The pineal total lipid profile and phospholipid molecular species distribution altered by n-3 deficiency were evaluated in parallel. In pineal glands from n-3-deficient rats, an 87% reduction of 22:6n-3 (docosahexaenoic acid) was observed, and this decrease was accompanied by increases in 22:4n-6 (docosatetraenoic acid, 3-fold), 22:5n-6 (docosapentaenoic acid, 12-fold), and 20:4n-6 (arachidonic acid, 48%). The significant decrease of 22:6n-3 containing species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) was also evident. These decreases in 22:6n-3 containing PL species were compensated by substantial accumulations of 22:4n-6 or 22:5n-6 and slight increases in 20:4n-6 containing PL species in PC and PE. In PS, however, the accumulation of n-6 species was not adequate to compensate for the loss of 22:6n-3 species. N-3 deficiency significantly reduced non-esterified 20:4n-6 and 22:6n-3 levels in pineals (25% and 65%, respectively). Concomitantly, the endogenous 12-HETE level decreased by 35% in deficient pineals. In contrast, n-3 deficiency led to a more than 60% increase in the daytime pineal melatonin level. In conclusion, n-3 fatty acid deficiency not only has profound effects on pineal lipid profiles but also on pineal biochemical activities. These results suggest that n-3 fatty acids may play a critical role in regulating pineal function.
Animals↗
Molecular species analysis of phospholipids.
The elucidation of phospholipid molecular species composition provides detailed structural information concerning various lipids and thus offers descriptions of crucial determinants of membrane physical and biological properties. Various methods differing in labor intensity, mode of separation and detection, type of calibration, as well as other factors, have been published. Thus precision and accuracy are expected to vary considerably between methods. Qualitative and quantitative aspects of different procedures for molecular species analysis of individual phospholipid classes are discussed in this review. Special emphasis has been given to the characterization of biological tissue samples.
Animals↗
Effect of mutations in vesicle-associated membrane protein (VAMP) on the assembly of multimeric protein complexes.
The assembly of multimeric protein complexes that include vesicle-associated membrane protein 2 (VAMP-2) and the plasma membrane proteins syntaxin 1A and synaptosome-associated protein of 25 kDa (SNAP-25) are thought to reflect the biochemical correlates of synaptic vesicle targeting, priming, or fusion. Using a variety of protein-protein interaction assays and a series of deletion and point mutations, we have investigated the domains of VAMP-2 required for the formation of binary complexes with either syntaxin 1A or SNAP-25 and ternary complexes with both syntaxin 1A and SNAP-25. Deletions within the central conserved domain of VAMP-2 eliminated binding to either syntaxin 1A or both syntaxin 1A and SNAP-25. Although all of the deletion mutants were able to form ternary complexes, only some of these complexes were resistant to denaturation in sodium dodecyl sulfate. These results demonstrate that cooperative interactions result in the formation of at least two biochemically distinct classes of ternary complex. Two point mutations previously shown to have effects on the intracellular trafficking of VAMP-2 (M46A, reduced endocytosis and sorting to synaptic vesicles; N49A, enhanced sorting to synaptic vesicles) lie within a domain required for both syntaxin 1A and SNAP-25 binding. Syntaxin 1A and SNAP-25 binding was reduced by the M46A mutation and enhanced by the N49A mutation, suggesting that a correlation exists between the membrane-trafficking phenotype of the two VAMP-2 point mutants and their competence to form complexes with either syntaxin 1A or SNAP-25.
Animals↗
The effects of low dietary levels of polyunsaturates on alcohol-induced liver disease in rhesus monkeys.
Rhesus monkeys that were maintained on a diet containing low, yet adequate, amounts of vitamins C and E and in which linoleate and linolenate represented 1.4% and 0.08% of the total caloric intake, respectively, developed liver fibrosis after consuming alcohol (mean, 2.6 g kg(-1) d[-1]) over a period of 3 years. In the liver, several polyunsaturated fatty acids including 18:2n6, 20:4n6, and 22:6n3 decreased compared with dietary controls, and similar findings were also observed in plasma lipoproteins and erythrocytes. The amount of alcohol consumed correlated positively with plasma lipid peroxidation products, 4-hydroxynonenal (4-HNE) and 8-isoprostane F2alpha, and negatively with 20:4n6 and 22:6n3 levels. These findings imply that alcoholics who also have a marginal intake of essential fatty acids and antioxidants in their diets may be at an increased risk of developing liver disease.
Aldehydes↗
Association of human herpes virus 6 (HHV-6) with multiple sclerosis: increased IgM response to HHV-6 early antigen and detection of serum HHV-6 DNA.
Viruses have long been suggested to be involved in the etiology of multiple sclerosis (MS). This suggestion is based on (1) epidemiological evidence of childhood exposure to infectious agents and increase in disease exacerbations with viral infection; (2) geographic association of disease susceptibility with evidence of MS clustering; (3) evidence that migration to and from high-risk areas influences the likelihood of developing MS; (4) abnormal immune responses to a variety of viruses; and (5) analogy with animal models and other human diseases in which viruses can cause diseases with long incubation periods, a relapsing-remitting course, and demyelination. Many of these studies involve the demonstration of increased antibody titers to a particular virus, whereas some describe isolation of virus from MS material. However, no virus to date has been definitively associated with this disease. Recently, human herpesvirus 6 (HHV-6), a newly described beta-herpes virus that shares homology with cytomegalovirus (CMV), has been reported to be present in active MS plaques. In order to extend these observations, we have demonstrated increased IgM serum antibody responses to HHV-6 early antigen (p41/38) in patients with relapsing-remitting MS (RRMS), compared with patients with chronic progressive MS (CPMS), patients with other neurologic disease (OND), patients with other autoimmune disease (OID), and normal controls. Given the ubiquitous nature of this virus and the challenging precedent of correlating antiviral antibodies with disease association, these antibody studies have been supported by the detection of HHV-6 DNA from samples of MS serum as a marker of active viral infection.
Antigens, Viral↗
Retinal and brain accretion of long-chain polyunsaturated fatty acids in developing felines: the effects of corn oil-based maternal diets.
A study was carried out in domestic felines to determine whether corn oil-based maternal diets are an adequate source of essential fatty acids to support normal accumulation of long-chain polyunsaturated fatty acids in the brains and retinas of offspring and whether these diets have any subsequent effect on visual function. Female domestic felines were acclimated to one of six different defined diets 1 mo before mating and maintained on the diets throughout pregnancy and lactation. Four diets contained only corn and hydrogenated coconut oils as their source of fat in ratios of 1:9, 3:7, 6:4, and 9:1, respectively. Two reference diets also contained the long-chain polyunsaturated fatty acids arachidonate (20:4n-6) and docosahexaenoate (22:6n-3). When the offspring were 8 wk old, electroretinograms were obtained and the a- and b-wave implicit times were determined. The results showed that animals raised in litters in which the maternal diets were devoid of 20:4n-6 and 22:6n-3 had an increase in a- and b-wave implicit times compared with the controls. In the rod outer segments and brains of these animals, there were lower amounts of 22:6n-3 and higher amounts of long-chain n-6 polyunsaturated fatty acids compared with control animals. These findings showed that although corn oil-based diets were capable of maintaining 20:4n-6 concentrations in the developing brain and retina, only those diets containing 22:6n-3 could support a high accumulation of docosahexaenoic acid in these tissues. Moreover, low amounts of 22:5n-6 in the brains of animals in all of the corn oil-diet groups suggested that young felines have a low biosynthetic capacity to produce this fatty acid or 22:6n-3. These findings suggest that in juvenile felines, maintenance of 22:6n-3 status in the nervous system is important for optimal retinal function.
Animals↗
Microcephaly and intracranial calcification: two new cases.
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Abnormalities, Multiple↗
Do plasma polyunsaturates predict hostility and depression?
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Adult↗
[Acute thrombosis of the portal system. Treatment with alteplase and heparin or with heparin alone in 10 patients].
OBJECTIVES: We report the efficacy of alteplase (a recombinant tissue plasminogen activator) with heparin or heparin alone in the treatment of acute thrombosis of the portal venous system. METHODS: Ten consecutive patients with acute portal venous system thrombosis were studied. Five patients were treated with alteplase and heparin, and the remaining 5 patients, who were asymptomatic or had a contraindication to alteplase, were treated with heparin alone. RESULTS: In 3 of the 5 patients treated with alteplase, ultrasonography showed total resolution of the thrombus; the remaining 2 had partial resolution of the thrombus. In 4 of the 5 patients treated with heparin alone, ultrasonography showed total resolution of the thrombus, and no change in one. No bleeding occurred. CONCLUSION: Treatment with heparin can result in complete recanalisation of acute portal venous system thrombosis. These data suggest that combined therapy with systemic alteplase does not increase the efficacy of heparin.
Acute Disease↗
Risks of cholesterol-lowering therapies.
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Anticholesteremic Agents↗
Cell lines expressing an acetylcholine release mechanism; correction of a release-deficient cell by mediatophore transfection.
Several neuronal and non-neuronal cell lines express a Ca(2+)-dependent mechanism of transmitter release that can be demonstrated after loading the cells with acetylcholine during culture. In contrast, a particular cell line, the neuroblastoma N18TG-2, was found to be deficient for release. We transfected N18TG-2 cells with a plasmid encoding Torpedo mediatophore, a protein able to translocate acetylcholine in response to calcium. The N18TG-2 cells expressed the Torpedo protein which reached their plasma membrane. At the same time, these cells acquired a Ca(2+)-dependent quantal release mechanism similar to the one naturally expressed by other cell lines. Hence, the presence of mediatophore in the plasma membrane seems essential for quantal release.
Acetylcholine↗
High-performance liquid chromatography method with light-scattering detection for measurements of lipid class composition: analysis of brains from alcoholics.
A high-performance liquid chromatographic method with evaporative light-scattering detection was developed for the analysis of intact lipid classes in nervous tissue. The method had the ability to resolve plasmalogen-phosphatidyl-ethanolamine and diacyl-phosphatidylethanolamine along with other major phospholipid classes in a single run. This technique was employed for the investigation of the effects of chronic alcohol consumption on the membrane lipid class composition of human brains (alcoholics, n = 13; controls, n = 11). Measurements were performed on cholesterol, cerebrosides, sulfatides, phospholipids and sphingolipids in total lipid extracts of white matter, gray matter and cerebellar regions of human brains. No significant differences in the lipid class composition between the groups were observed.
Alcoholism↗