Hostname: page-component-586b7cd67f-gb8f7 Total loading time: 0 Render date: 2024-11-23T03:34:27.225Z Has data issue: false hasContentIssue false

Maternal dietary 22: 6n-3 is more effective than 18: 3n-3 in increasing the 22: 6n-3 content in phospholipids of glial cells from neonatal rat brain

Published online by Cambridge University Press:  08 March 2007

Raffick A. R. Bowen
Affiliation:
Nutrition and Metabolism Research Group, Department of Agricultural, Food and Nutritional Science University of Alberta, Edmonton, Alberta T6G 2P5, Canada
Michael T. Clandinin*
Affiliation:
Nutrition and Metabolism Research Group, Department of Agricultural, Food and Nutritional Science University of Alberta, Edmonton, Alberta T6G 2P5, Canada Department of Medicine, University of Alberta, Edmonton, Alberta T6G 2P5, Canada
*
*Corresponding author: Dr M. Thomas Clandinin, fax +1 (780) 492-8855, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

One of the debates in infant nutrition concerns whether dietary 18: 3n-3 (linolenic acid) can provide for the accretion of 22: 6 n-3 (docosahexaenoic acid, DHA) in neonatal tissues. The objective of the present study was to determine whether low or high 18: 3 n-3 v. preformed 22: 6 n-3 in the maternal diet enabled a similar 22: 6 n-3 content in the phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and phosphatidylserine (PS) of glial cells from whole brain (cerebrum and cerebellum) of 2-week-old rat pups. At parturition, the dams were fed semi-purified diets containing either increasing amounts of 18: 3 n-3 (18: 2 n-6 to 18: 3 n-3 fatty acid ratio of 7·8: 1, 4·4: 1 or 1: 1), preformed DHA, or preformed 20: 4 n-6 (arachidonic acid)+DHA. During the first 2 weeks of life, the rat pups from the respective dams received only their dam's milk. The fatty acid composition of the pups' stomach contents (dam's milk) and phospholipids from glial cells were quantified. The 20: 4n-6 and 22: 6 n-3 content in the stomach from rat pups at 2 weeks of age reflected the fatty acid composition of the dam's diet. The 20: 4n-6 content of PE and PS in the glial cells was unaffected by maternal diet treatments. Preformed 22: 6 n-3 in the maternal diet increased the 22: 6 n-3 content of glial cell PE and PS compared with maternal diets providing an 18: 2n-6 to 18: 3 n-3 fatty acid ratio of 7·8: 1, 4·4: 1 or 1: 1 (P<0·0001). There was no significant difference in the 20: 4 n-6 and 22: 6 n-3 content of glial cell PC and PI among maternal diet treatments. It was concluded that maternal dietary 22: 6n-3 is more effective than low or high levels of maternal dietary 18: 3 n-3 at increasing the 22: 6 n-3 content in PE and PS of glial cells from the whole brain of rat pups at 2 weeks of age. The findings from the present study have important implications for human infants fed infant formulas that are devoid of 22: 6 n-3.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

Abedin, L, Lien, EL, Vingrys, AJ & Sinclair, AJ (1999) The effects of dietary α-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig. Lipids 34, 475482.Google Scholar
Aid, S, Vancassel, S, Poumes-Ballihaut, C, Chalon, S, Guesnet, P & Lavialle, M (2003) Effect of a diet-induced n-3 PUFA depletion on cholinergic parameters in the rat hippocampus. J Lipid Res 44, 15451551.Google Scholar
Akbar, M & Kim, HY (2002) Protective effects of docosahexaenoic acid in staurosporine-induced apoptosis: involvement of phosphatidylinositol-3 kinase pathway. J Neurochem 82, 655665.CrossRefGoogle ScholarPubMed
Anderson, G & Connor, WE (1988) Uptake of fatty acids by developing brain. Lipids 23, 286290.Google Scholar
Anderson, RE, Benolken, RM, Dudley, PA, Landis, DJ & Wheeler, TG (1974) Polyunsaturated fatty acids of photoreceptor membranes. Exp Eye Res 18, 205213.Google Scholar
Barcelo-Coblijn, G, Hogyes, E, Kitajka, K, Puskas, LG, Zvara, A, Hackler, L, Jr, Nvakas, C, Penke, Z, Farkas T (2003) Modification by docosahexaenoic acid of age-induced alterations in gene expression and molecular composition of rat brain phospholipids. Proc Natl Acad Sci USA 100, 1132111326.Google Scholar
Bazinet, RP, McMillan, EG & Cunnane, SC (2003a) Dietary alpha-linolenic acid increases the n-3 PUFA content of sow's milk and the tissues of the suckling piglet. Lipids 38, 10451049.Google Scholar
Bazinet, RP, McMillan, EG, Seebaransingh, R, Hayes, AM & Cunnane, SC (2003b) Whole-body beta-oxidation of 18: 2 omega6 and 18: 3 omega3 in the pig varies markedly with weaning strategy and dietary 18: 3 omega3. J Lipid Res 44, 314319.Google Scholar
Bell, RM & Burns, DJ (1991) Lipid activation of protein kinase C. J Biol Chem 266, 46614664.Google Scholar
Bernhart, JT & Sprecher, H (1975) Studies to determine the role rates of chain elongation and desaturation in regulating the unsaturated fatty acid composition of rat liver lipids. Biochim Biophys Acta 398, 354363.Google Scholar
Bernoud, N, Fenart, L, Bénistant, C, Pageaux, JF, Dehouck, MP, Molière, P (1998) Astrocytes are mainly responsible for the polyunsaturated fatty acid enrichment in blood-brain barrier endothelial cells in vitro. J Lipid Res 39, 18161824.CrossRefGoogle ScholarPubMed
Birch, EE, Garfield, S & Hoffman, DR (2000) A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Dev Med Child Neurol 42, 174181.Google Scholar
Borghese, CM, Gomez, RA & Ramirez, OA (1993) Phosphatidylserine increases hippocampal synaptic efficacy. Brain Res Bull 31, 697700.CrossRefGoogle ScholarPubMed
Bourre, JM, Dinh, L, Boithias, C, Dumont, O, Piciotti, M & Cunnane, S (1997) Possible role of the choroid plexus in the supply of brain tissue with polyunsaturated fatty acids. Neurosci Lett 224, 14.Google Scholar
Bourre, JM, Durand, G, Pascal, G & Youyou, A (1989) Brain cell and tissue recovery in rats made deficient in n-3 fatty acids by alteration of dietary fat. J Nutr 119, 1522.CrossRefGoogle ScholarPubMed
Bourre, JM, Piciotti, M & Dumont, O (1990) Delta-6-desaturase in brain and liver during development and aging. Lipids 25, 354356.CrossRefGoogle ScholarPubMed
Bowen, RAR & Clandinin, MT (2000) High dietary C18: 3 n -3 increases the C18: 3 n -3 but not the 22: 6 n -3 content in the whole body, brain, skin, epididymal fat pads, and muscles of suckling rat pups. Lipids 35, 389394.CrossRefGoogle Scholar
Bowen, RA & Clandinin, MT (2002) Dietary low linolenic acid compared with docosahexaenoic acid alters synaptic plasma membrane phospholipid fatty acid composition and sodium-potassium ATPase kinetics in developing rats. J Neurochem 83, 764774.Google Scholar
Bowen, RAR, Wierzbicki, AA & Clandinin, MT (1999) Does increasing dietary C18: 3 n -3 acid content increase the docosahexaenoic acid content of phospholipids in neuronal cells of neonatal rats?. Pediatr Res 45, 815819.CrossRefGoogle Scholar
Breckenridge, WC, Gombos, G & Morgan, IG (1972) The lipid composition of adult rat brain synaptosomal membranes. Biochim Biophys Acta 266, 695707.Google Scholar
Calderon, F & Kim, HY (2004) Docosahexaenoic acid promotes neurite growth in hippocampal neurons. J Neurochem 90, 979988.CrossRefGoogle ScholarPubMed
Carlson, SE & Neuringer, M (1999) Polyunsaturated fatty acid status and neurodevelopment: a summary and critical analysis of the literature. Lipids 34, 171178.Google Scholar
Carlson, SE, Werkman, SH & Tolley, EA (1992) First year growth of preterm infants fed standard compared to marine oil n-3 supplemented formula. Lipids 27, 901907.CrossRefGoogle ScholarPubMed
Carlson, SE, Werkman, SH & Tolley, EA (1996) Effect of long-chain n-3 fatty acid supplementation on visual acuity and growth of preterm infants with and without bronchopulmonary dysplasia. Am J Clin Nutr 63, 687697.CrossRefGoogle ScholarPubMed
Carrie, I, Clément, M, de Javel, D, Francès, H & Bourre, JM (1999) Learning deficits in first generation OF1 mice deficient in (n-3) polyunsaturated fatty acids do not result from visual alteration. Neurosci Lett 266, 6972.CrossRefGoogle Scholar
Carrie, I, Guesnet, P, Bourre, JM & Frances, H (2000) Diets containing long-chain n-3 polyunsaturated fatty acids affect behaviour differently during development than ageing in mice. Brit J Nutr 83, 439447.Google ScholarPubMed
Chalon, S, Delion-Vancassel, S, Belzung, C, Guilloteau, D, Leguisquet, AM & Besnard, JC (1998) Dietary fish oil affects monoaminergic neurotransmission and behavior in rats. J Nutr 128, 25122519.Google Scholar
Champeil-Potokar, G, Denis, I, Goustard-Langelier, B, Alessandri, JM, Guesnet, P & Lavialle, M (2004) Astrocytes in culture require docosahexaenoic acid to restore the n-3/n-6 polyunsaturated fatty acid balance in their membrane phospholipids. J Neurosci Res 75, 96106.CrossRefGoogle ScholarPubMed
Clandinin, MT (1997) Influence of diet fat on membranes. In Membrane and Cell Signaling. Principles of Medical Biology, vol. 7A. pp. 93119Greenwich: JAI Press.CrossRefGoogle Scholar
Clandinin, MT, Chappell, JE, Leong, S, Heim, T, Swyer, PR & Chance, GW (1980a) Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. Early Hum Dev 4, 121129.Google Scholar
Clandinin, MT, Chappell, JE, Leong, S, Heim, T, Swyer, PR & Chance, GW (1980b) Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements. Early Human Dev 4, 131138.CrossRefGoogle ScholarPubMed
Clandinin, MT, Chappell, JE, Van Aerde, JEE (1989) Requirements of newborn infants for long-chain polyunsaturated fatty acids. Acta Paediatr Scand 351, 6371.CrossRefGoogle ScholarPubMed
Cotman, C, Blank, ML, Moehl, A & Snyder, F (1969) Lipid composition of synaptic plasma membranes isolated from rat brain by zonal centrifugation. Biochemistry 8, 46064612.CrossRefGoogle ScholarPubMed
Cunnane, SC, Keeling, PW, Thompson, RP & Crawford, MA (1984) Linoleic acid and arachidonic acid metabolism in human peripheral blood leucocytes: comparison with the rat. Br J Nutr 51, 209217.Google Scholar
Cunnane, SC, Menard, CR, Likhodii, SS, Brenna, JT & Crawford, MA (1999) Carbon recycling into de novo lipogenesis is a major pathway in neonatal metabolism of linoleate and α-linolenate. Prostaglandins Leukot Essent Fatty Acids 60, 387392.Google Scholar
Cunnane, SC, Williams, SC, Bell, JD, Brookes, S, Craig, K, Iles, RA & Crawford, MA (1994) Utilization of uniformly labeled 13C-polyunsaturated fatty acids in the synthesis of long-chain fatty acids and cholesterol accumulating in the neonatal rat brain. J Neurochem 62, 24292436.CrossRefGoogle ScholarPubMed
DeLany, JP, Windhauser, MM, Champagne, CM & Bray, GA (2000) Differential oxidation of individual dietary fatty acids in humans. Am J Clin Nutr 72, 905911.CrossRefGoogle ScholarPubMed
De La, Presa, Owens, S & Innis, SM (1999) Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in frontal cortex caused by a linoleic and alpha-linolenic acid deficient diet in formula-fed piglets. J Nutr 129, 20882093.Google Scholar
Delion, S, Chalon, S, Herault, J, Guilloteau, D, Besnard, JC & Durand, G (1994) Chronic dietary α-linoleic acid deficiency alters dopaminergic and serotinergic neurotransmitters in rats. J Nutr 124, 24662476.CrossRefGoogle Scholar
Delton-Vandenbroucke, I, Grammas, P & Anderson, RE (1997) Polyunsaturated fatty acid metabolism in retinal and cerebral microvascular endothelial cells. J Lipid Res 38, 147159.Google Scholar
Dhopeshwarkar, GA & Subramanian, C (1976) Intracranial conversion of linoleic acid to arachidonic acid: evidence for lack of delta-8 desaturase in the brain. J Neurochem 26, 11751179.Google Scholar
Dobbing, J & Sands, J (1979) Comparative aspects of the brain growth spurt. Early Hum Dev 3, 7983.Google Scholar
Edmond, J, Tami, AH, Rose, AK, Bergner, EA & Lee, WNP (1998) Fatty acid transport and utilization for the developing brain. J Neurochem 70, 12271234.CrossRefGoogle ScholarPubMed
Enslen, M, Milon, H & Malnoe, A (1991) Effect of low intake of n-3 fatty acids during development on brain phospholipid fatty acid composition and exploratory behavior in rats. Lipids 26, 203208.Google Scholar
Ferdinandusse, S, Denis, S, Mooijer, PAW, Zhang, Z, Reddy, JK, Spector, AA & Wanders, RJ (2001) Identification of the peroxisomal-oxidation enzymes involved in the biosynthesis of docosahexaenoic acid. J Lipid Res 42, 19871995.Google Scholar
Folch, J, Lee, M, Sloane-Stanley, GH (1957) A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226, 497506.Google Scholar
Foot, M, Cruz, TG & Clandinin, MT (1982) Influence of dietary fat on the lipid composition of rat brain synaptosomal and microsomal membranes. Biochem J 208, 631641.Google Scholar
Frances, H, Coudereau, JP, Sandouk, P, Clement, M, Monier, C & Bourre, JM (1996) Influence of a dietary alpha-linolenic acid deficiency on learning in the Morris water maze and on the effects of morphine. Eur J Pharmacol 298, 217225.Google Scholar
Fu, Z & Sinclair, AJ (2000) Novel pathway of metabolism of alpha-linolenic acid in the guinea pig. Pediatr Res 47, 414417.Google Scholar
Garcia, M, Ward, G, Ma, YC, Salem, N, Jr, Kim HY (1998) Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain microsomes and C6 glioma cells. J Neurochem 70, 2430.Google Scholar
Gerbi, A, Zerouga, M, Debray, M, Durand, G, Chanez, C & Bourre, J (1994) Effect of fish oil diet on fatty acid composition of phospholipids of brain membranes and on kinetic properties of Na, K-ATPase isoenzymes of weaned and adult rats. J Neurochem 62, 15601569.Google Scholar
Ghosh, S, Strum, JC, Sciorra, VA, Daniel, L & Bell, RM (1996) Raf-1 kinase possesses distinct binding domains for phosphatidylserine and phosphatic acid. J Biol Chem 271, 84728480.Google Scholar
Green, P & Yavin, E (1995) Modulation of fetal rat brain and liver phospholipid content by intraamniotic ethyl docosahexaenoate administration. J Neurochem 65, 25552560.Google Scholar
Green, P & Yavin, E (1996a) Fatty acid composition of late embryonic and early postnatal rat brain. Lipids 31, 52355238.Google Scholar
Green, P & Yavin, E (1996b) Natural and accelerated docosahexaenoic acid accumulation in the prenatal rat brain. Lipids 31, S235S238.CrossRefGoogle ScholarPubMed
Green, P & Yavin, E (1998) Mechanism of docosahexaenoic acid accretion in the fetal brain. J Neurosci Res 52, 129136.Google Scholar
Hamilton, J, Greiner, R, Salem, N, Jr, Kim HY (2000) N-3 fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues. Lipids 35, 863869.Google Scholar
Horrobin, DF, Huang, YS, Cunnane, SC & Manku, MS (1984) Essential fatty acid in plasma, red blood cells and liver phospholipids in common laboratory animals as compared to humans. Lipids 19, 806811.Google Scholar
Huster, D, Arnold, K & Gawrisch, K (1998) Influence of docosahexaenoic acid and cholesterol on lateral lipid organization in phospholipid mixtures. Biochemistry 37, 1729917308.CrossRefGoogle ScholarPubMed
Ikemoto, A, Kobayashi, T, Emoto, K, Umeda, M, Watanabe, S & Okuyama, H (1999) Effects of docosahexaenoic and arachidonic acids on the synthesis and distribution of aminophospholipids during neuronal differentiation of PC12 cells. Arch Biochem Biophys 364, 6774.Google Scholar
Innis, SM (1991) Essential fatty acids in growth and development. Prog Lipid Res 30, 39103.Google Scholar
Innis, SM, de La, Presa & Owens, S (2001) Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain. J Nutr 131, 118122.CrossRefGoogle ScholarPubMed
Innis, SM & Dyer, RA (2002) Brain astrocyte synthesis of docosahexaenoic acid from n-3 fatty acids is limited at the elongation of docosapentaenoic acid. J Lipid Res 43, 15291536.Google Scholar
Jacobson, SW (1999) Assessment of long-chain polyunsaturated fatty acid nutritional supplementation on infant neurobehavioral development and visual acuity. Lipids 34, 151160.CrossRefGoogle ScholarPubMed
Jump, DB (2002) The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 277, 87558758.CrossRefGoogle ScholarPubMed
Jumpsen, JA, Lien, E, Goh, YK & Clandinin, MT (1997a) Diets varying in n-3 and n-6 fatty acid content produce differences in phosphatidylethanolamine and phosphatidylcholine fatty acid composition during development of neuronal and glial cells in rats. J Nutr 127, 724731.Google Scholar
Jumpsen, JA, Lien, E, Goh, YK & Clandinin, MT (1997b) During neuronal and glial cell development diet n-6 to n-3 fatty acid ratio alters the fatty acid composition of phosphatidylinositol and phosphatidylserine. Biochim Biophys Acta 1347, 4050.Google Scholar
Kim, HY, Akbar, M, Lau, A & Edsall, L (2000) Inhibition of neuronal apoptosis by docosahexaenoic acid (22: 6 n -3): Role of phosphatidylserine in antiapoptotic effect. J Biol Chem 275, 3521535223.CrossRefGoogle Scholar
Kinsella, JE, Lokesh, B, Broughton, S & Whelan, JW (1990) Dietary polyunsaturated fatty acids and eicosanoids: potential effects on the modulation of inflammatory and immune cells: an overview. J Nutr 6, 2444.Google Scholar
Kishimoto, Y, Davies, WE & Radin, NS (1965) Developing rat brain: changes in cholesterol, galactolipids, and the individual fatty acids of gangliosides and glycerophosphatides. J Lipid Res 6, 532536.Google Scholar
Kita, Y, Kimura, KD & Kobayashi, M (1998) Microinjection of activated phosphatidylinositol-3 kinase induces process outgrowth in rat PC12 cells through the Rac-JNK signal transduction pathway. J Cell Sci 111, 907915.CrossRefGoogle ScholarPubMed
Kitajka, K, Sinclair, AJ, Weisinger, RS, Weisinger, HS, Mathai, M, Jayasooriya, AP, Halver, JE & Puskas, LG (2004) Effects of dietary omega-3 polyunsaturated fatty acids on brain gene expression. Proc Natl Acad Sci USA 101, 1093110936.CrossRefGoogle ScholarPubMed
Kobayashi, M, Nagata, S & Kita, Y (1997) Expression of a constitutively active phosphatidylinositol 3-kinase induces process formation in rat PC12 cells. Use of Cre/loxP recombination system. J Biol Chem 272, 1608916092.CrossRefGoogle ScholarPubMed
Kodas, E, Galineau, L, Bodard, S, Vancassel, S, Guilloteau, D, Besnard, JC & Chalon, S (2004) Serotoninergic neurotransmission is affected by n-3 polyunsaturated fatty acids in the rat. J Neurochem 89, 695702.Google Scholar
Kuo, WL, Abe, M, Rhee, J, Eves, EM, McCarthy, SA, Yan, M, Templeton, DJ, McMahon, M & Rosner, MR (1996) Raf, but not MEK or ERK, is sufficient for differentiation of hippocampal neuronal cells. Mol Cell Biol 16, 14581470.CrossRefGoogle ScholarPubMed
Kurvinen, JP, Kuksis, A, Sinclair, AJ, Abedin, L & Kallio, H (2000) The effect of low-linolenic acid diet on glycerophospholipid molecular species in guinea pig brain. Lipids 35, 10011009.Google Scholar
Lamptey, MS & Walker, BL (1976) A possible essential role for dietary linolenic acid in the development of the young rat. J Nutr 106, 8693.Google Scholar
Levi, deStein, M, Medina, DeRobertis, JHED (1989) In vivo and in vitro modulation of central type of benzodiazepine receptors by phosphatidylserine. Mol Brain Res 5, 915.Google Scholar
Leyton, J, Drury, PJ & Crawford, MA (1987) Differential oxidation of saturated and unsaturated fatty acids in vivo in the rat. Br J Nutr 57, 383393.Google Scholar
Lien, EL, Boyle, FG, Yuhas, RJ & Kuhlman, CF (1994) Effect of maternal dietary C20: 4n-6 or C18: 2 n -6 acid on rat pup fatty acid profiles. Lipids 29, 5359.Google Scholar
Litman, BJ & Mitchell, DC (1996) A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids 31, S193S197.Google Scholar
Madsen, L, Froyland, L, Dyroy, E, Helland, K & Berge, R (1998) Docosahexaenoic and eicosapentaenoic acids are differently metabolized in rat. J Lipid Res 39, 583593.Google Scholar
Martinez, M (1989) Polyunsaturated fatty acids changes suggesting a new enzymatic defect in Zellweger syndrome. Lipids 24, 261265.CrossRefGoogle ScholarPubMed
Menard, CR, Goodman, KJ, Corso, TN, Brenna, JT & Cunnane, SC (1998) Recycling of carbon into lipids synthesized de novo is a quantitatively important pathway of alpha-[U-13C] linolenate utilization in the developing rat brain. J Neurochem 71, 21512158.Google Scholar
Mitchell, DC & Litman, BJ (1998) Molecular order and dynamics in bilayers consisting of highly polyunsaturated phospholipids. Biophys J 74, 879891.Google Scholar
Moore, SA (1993) Cerebral endothelium and astrocytes cooperate in supplying docosahexaenoic acid to neurons. Adv Exp Med Biol 331, 229233.Google Scholar
Moore, SA (2001) Polyunsaturated fatty acid synthesis and release by brain-derived cells in vitro. J Mol Neurosci 16, 195200.Google Scholar
Moore, SA, Yoder, E, Murphy, S, Dutton, GR & Spector, AA (1991) Astrocytes, not neurons, produce docosahexaenoic acid (22: 6 n -3) and arachidonic acid (20: 4n-6). J Neurochem 56, 518524.CrossRefGoogle Scholar
Moore, SA, Yoder, E & Spector, AA (1990) Role of the blood-brain barrier in the formation of long-chain n-3 and n-6 fatty acids from essential fatty acid precursors. J Neurochem 55, 391402.Google Scholar
Morgane, PJ, Austin-LaFrance, R, Bronzino, J, Tonkiss, J, Diaz-Cintra, S, Cintra, L, Kemper, T & Galler, JR (1993) Prenatal malnutrition and development of the brain. Neurosci Biobehav Rev 17, 91128.Google Scholar
Moriguchi, T, Greiner, RS, Salem, N Jr (2000) Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem 75, 25632573.Google Scholar
Morrison, WR & Smith, LM (1964) Preparation of fatty acid methyl esters and dimethyl-acetals from lipids with boron fluoride-methanol. J Lipid Res 5, 600608.CrossRefGoogle Scholar
Murthy, M, Hamilton, J, Greiner, RS, Moriguchi, T, Salem, N, Kim, H-Y Jr (2002) Differential effects of n-3 fatty acid deficiency on phospholipid molecular species composition in the rat hippocampus. J Lipid Res 43, 611617.Google Scholar
Nouvelot, A, Bourre, JM, Sezille, G, Dewailly, P & Jaillard, J (1983) Changes in the fatty acid patterns of brain phospholipids during development of rats fed peanut or rapeseed oil, taking into account differences between milk and maternal food. Ann Nutr Metab 27, 173181.CrossRefGoogle ScholarPubMed
Nouvelot, A, Delbart, C & Bourre, JM (1986) Hepatic metabolism of dietary alpha-linolenic acid in suckling rats, and its possible importance in polyunsaturated fatty acid uptake by the brain. Ann Nutr Metab 30, 316323.Google Scholar
O'Brien, JS & Sampson, EL (1965) Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter and myelin. J Lipid Res 6, 545551.Google Scholar
Okuyama, H, Kobayashi, T & Watanabe, S (1997) Dietary fatty acids-the n-6/n-3 balance and chronic elderly diseases. Excess linoleic acid and relative n-3 deficiency syndrome seen in Japan. Prog Lipid Res 35, 409457.CrossRefGoogle Scholar
Puskas, LG, Kitajka, K, Nyakas, C, Barcelo-Coblijn, G & Farkas, T (2003) Short-term administration of omega 3 fatty acids from fish oil results in increased transthyretin transcription in old rat hippocampus. Proc Natl Acad Sci USA 100, 15801585.CrossRefGoogle ScholarPubMed
Ravel, D, Chambaz, J, Pepin, D, Manier, MC & Bereziat, G (1985) Essential fatty acid interconversion during gestation in the rat. Biochim Biophys Acta 833, 161164.Google Scholar
Salem, N, Niebylski, CD Jr (1995) The nervous system has an absolute molecular species requirement for proper function. Mol Membr Biol 12, 131134.Google Scholar
Salem, N, Jr, Litman, B, Kim, Gawrisch, HYK (2001) Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids 36, 945959.Google Scholar
Salem, N, Jr, Serpentino, P, Puskin, Abood, JSLG (1980) Preparation and spectroscopic characterization of molecular species of brain phosphatidylserines. Chem Phys Lipids 27, 289304.Google Scholar
Salem, N, Jr, Wegher, B, Mena, Uauy, PR (1996) Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci USA 93, 4954.Google Scholar
Sanders, TA & Rana, SK (1987) Comparison of the metabolism of linoleic and linolenic acids in the fetal rat. Ann Nutr Metab 31, 349353.CrossRefGoogle Scholar
SAS Institute Inc. (1988) SAS/STAT User's Guide Release 6.11 Edition.Cary, NC:SAS Institute Inc.Google Scholar
Sastry, PS (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24, 69176.CrossRefGoogle Scholar
Sauerwald, TU, Hachey, DL, Luijendijik, IHT, Boerlage, A, Degerhart, HJ & Sauer, PJJ (1996) New insights into the metabolism of long chain polyunsaturated fatty acids during infancy. Eur J Med Res 2, 8892.Google Scholar
Sellinger, OZ & Azcurra, JM (1974) Bulk separation of neuronal cell bodies and glial cells in the absence of added digestive enzymes. In Research Methods in Neurochemistry, pp. 338 [Marks, N, Rodnight, R, editors]. New York: Plenum Press.Google Scholar
Sheaff-Greiner, RC, Zhang, Q, Goodman, KJ, Giussani, DA, Nathanielsz, PW & Brenna, JT (1996) Linoleate, α-linolenate, and docosahexaenoate recycling into saturated and mono unsaturated fatty acids is a major pathway in pregnant or lactating adults and fetal or infant rhesus monkeys. J Lipid Res 37, 26752686.CrossRefGoogle ScholarPubMed
Sinclair, AJ (1975) Incorporation of radioactive polyunsaturated fatty acids into liver and brain of developing rat. Lipids 10, 175184.CrossRefGoogle ScholarPubMed
Sinclair, AJ & Crawford, MA (1972) The accumulation of arachidonate and docosahexaenoate in developing rat brain. J Neurochem 19, 17531758.CrossRefGoogle ScholarPubMed
Spector, AA & Yorek, MA (1985) Membrane lipid composition and cellular function. J Lipid Res 26, 10151035.CrossRefGoogle ScholarPubMed
Sprecher, H (2000) Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim Biophys Acta 1486, 219231.Google Scholar
Sprecher, H, Chen, Q & Yin, FQ (1999) Regulation of the biosynthesis of 22: 5 n -6 and 22: 6 n -3: a complex intracellular process. Lipids 34, S153S156.CrossRefGoogle Scholar
Steel, RGD & Torrie, JH (1960) Principles and Procedures of Statistics, New York: McGraw-Hill.Google Scholar
Stubbs, CD & Smith, AD (1984) The modification of mammalian membrane polyunsaturated fatty acid composition in relation to membrane fluidity and function. Biochim Biophys Acta 779, 89137.Google Scholar
Sun, GY & Horrocks, LA (1970) The acyl and alk-1-enyl groups of the major phosphoglycerides from ox brain myelin and mouse brain microsomal, mitochondrial and myelin fractions. Lipids 5, 10061012.CrossRefGoogle ScholarPubMed
Sun, GY & Sun, AY (1974) Synaptosomal plasma membranes: acyl group composition of phosphoglycerides and (Na + +K + )-ATPase activity during essential fatty acid deficiency. J Neurochem 22, 1518.Google Scholar
Tinoco, J (1982) Dietary requirements and functions of alpha-linolenic acid in animals. Prog Lipid Res 21, 145.Google Scholar
Touchstone, JC, Chen, JC & Beaver, KM (1980) Improved separation of phospholipids in thin-layer chromatography. Lipids 15, 6162.Google Scholar
Tsutsumi, T, Yamauchi, E, Suzuki, E, Watanabe, S, Kobayashi, T & Okuyama, H (1995) Effect of a high alpha-linolenate and high linoleate diet on membrane-associated enzyme activities in rat brain-modulation of Na+, K+- ATPase activity at suboptimal concentrations of ATP. Biol Pharm Bull 18, 664670.CrossRefGoogle ScholarPubMed
Uauy, R, Mena, P, Wegher, B, Nieto, S, Salem, N Jr (2000) Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth. Pediatr Res 47, 127135.CrossRefGoogle ScholarPubMed
Ubl, JJ & Reiser, G (1997) Characteristics of thrombin-induced calcium signals in rat astrocytes. Glia 21, 361369.Google Scholar
Voss, AM, Reinhart, S, Sankarappa, S & Sprecher, H (1991) The metabolism of 7,10,13,16,19-docosapentaenoic acid to 4,7,10,13, 16,19-docosahexaenoic acid in rat liver is independent of a 4-desaturase. J Biol Chem 226, 1999520000.CrossRefGoogle Scholar
Wainwright, PE, Xing, HC, Girard, T, Parker, L & Ward, G (1998) Effects of dietary n-3 fatty acid deficiency on Morris water-maze performance and amphetamine-induced conditioned place preference in rats. Nutr Neurosci 1, 281293.Google Scholar
Wheeler, TG, Benolken, RM & Anderson, RE (1975) Visual membranes: specificity of fatty acid precursors for the electrical response to illumination. Science 188, 13121314.Google Scholar
Willard, DE, Harmon, SD & Kaduce, TL (2001) Docosahexaenoic acid synthesis from n-3 polyunsaturated fatty acids in differentiated rat brain astrocytes. J Lipid Res 42, 13681376.Google Scholar
Willard, DE, Harmon, SD, Kaduce, TL & Spector, AA (2002) Comparison of 20-, 22-, and 24-carbon n-3 and n-6 polyunsaturated fatty acid utilization in differentiated rat brain astrocytes. Prostaglandins Leukot Essent Fatty Acids 67, 99104.CrossRefGoogle Scholar
Willats, P, Forsyth, JS, Dimodugno, MK, Varma, S & Colvin, M (1998) Effects of long chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet 352, 688691.Google Scholar
Willatts, P & Forsyth, JS (2000) The role of long-chain polyunsaturated fatty acids in infant cognitive development. Prostaglandins Leukot Essent Fatty Acids 63, 95100.Google Scholar
Wood, KW, Qi, H, D'Arcangelo, G, Armstrong, RC, Roberts, TM & Halegoua, S (1993) The cytoplasmic raf oncogene induces a neuronal phenotype in PC12 cells: a potential role for cellular raf kinases in neuronal growth factor signal transduction. Proc Natl Acad Sci USA 90, 50165020.Google Scholar
Woods, J, Ward, G, Salem, N Jr (1996) Evaluation of high linolenate diets in the neonatal rat. Pediatr Res 40, 687–694.Google Scholar
Yamamoto, N, Saitoh, M, Moriuchi, A, Nomura, M & Okuyama, H (1987) Effect of dietary alpha-linolenate/linoleate balance on brain lipid compositions and learning ability of rats. J Lipid Res 28, 144151.Google Scholar
Yonekubo, A, Honda, S, Okano, M, Takahashi, K & Yamamoto, Y (1993) Dietary fish oil alters rat milk composition and liver and brain fatty acid composition of fetal and neonatal rats. J Nutr 123, 17031708.Google Scholar
Zhang, H, Hamilton, JH, Salem, N, Jr, Kim HY (1998) N-3 Fatty acid deficiency in the rat pineal gland: effects on phospholipid molecular species composition and endogenous 12-HETE and melatonin levels. J Lipid Res 39, 13971403.CrossRefGoogle Scholar
Zimmer, L, Vancassel, S, Cantagrel, S, Breton, P, Delamanche, S, Guilloteau, D, Durand, G & Chalon, S (2002) The dopamine mesocorticolimbic pathway is affected by deficiency in n-3 polyunsaturated fatty acids. Am J Clin Nutr 75, 662667.CrossRefGoogle ScholarPubMed