Hostname: page-component-6bf8c574d5-956mj Total loading time: 0 Render date: 2025-02-22T21:32:25.968Z Has data issue: false hasContentIssue false
  • English
  • Français

Dietary essential fatty acids and brain function: a developmental perspective on mechanisms

Published online by Cambridge University Press:  28 February 2007

Patricia E. Wainwright
Patricia E. Wainwright*
Affiliation:
Department of Health Studies and Gerontology, University of Waterloo, Waterloo, Ontario N2L 5H1, Canada
*
Corresponding author: Professor Patricia E. Wainwright, fax +1 519 746 2510, 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.

Brain development is a complex interactive process in which early disruptive events can have long-lasting effects on later functional adaptation. It is a process that is dependent on the timely orchestration of external and internal inputs through sophisticated intra- and intercellular signalling pathways. Long-chain polyunsaturated fatty acids (LCPUFA), specifically arachidonic acid and docosahexaenoic acid (DHA), accrue rapidly in the grey matter of the brain during development, and brain fatty acid (FA) composition reflects dietary availability. Membrane lipid components can influence signal transduction cascades in various ways, which in the case of LCPUFA include the important regulatory functions mediated by the eicosanoids, and extend to long-term regulation through effects on gene transcription. Our work indicates that FA imbalance as well as specific FA deficiencies can affect development adversely, including the ability to respond to environmental stimulation. For example, although the impaired water-maze performance of mice fed a saturated-fat diet improved in response to early environmental enrichment, the brains of these animals showed less complex patterns of dendritic branching. Dietary n-3 FA deficiency influences specific neurotransmitter systems, particularly the dopamine systems of the frontal cortex. We showed that dietary deficiency of n-3 FA impaired the performance of rats on delayed matching-to-place in the water maze, a task of the type associated with prefrontal dopamine function. We did not, however, find an association over a wider range of brain DHA levels and performance on this task. Some, but not all, studies of human infants suggest that dietary DHA may play a role in cognitive development as well as in some neurodevelopmental disorders; this possibility has important implications for population health.

Keywords

Essential fatty acidsArachidonic acidDocosahexaenoic acidBrain developmentAnimal models
Type
Meeting Report
Information
Proceedings of the Nutrition Society , Volume 61 , Issue 1 , February 2002 , pp. 61 - 69
Copyright
Copyright © The Nutrition Society 2002

References

Berger-Sweeney, J & Hohmann, CF (1997) Behavioral consequences of abnormal cortical development: insights into developmental disabilities. Behavioural Brain Research 86, 121–142.CrossRefGoogle ScholarPubMed
Birch, EE, Garfield, S, Hoffman, DR, Uauy, R & Birch, DG (2000) A randomized controlled trial of early dietary supply of long-chain polyunsaturated fatty acids and mental development in term infants. Developmental Medicine and Child Neurology 42, 174–181.Google ScholarPubMed
Black, JE (1998) How a child builds its brain: some lessons from animal studies of neural plasticity. Preventive Medicine 27, 168–171.CrossRefGoogle ScholarPubMed
Black, JE, Jones, TA, Nelson, CA & Greenough, WT (1998) Neural plasticity and the developing brain. In The Handbook of Child and Adolescent Psychiatry, vol. 6, pp. 31–53 [Alessi, N, Coyle, JT, Harrison, SI and Eth, S, editors]. New York: John Wiley & Sons.Google Scholar
Carlson, SE & Neuringer, M (1999) Polyunsaturated fatty acid status and neurodevelopment: a summary and critical analysis of the literature. Lipids 34, 171–178.CrossRefGoogle ScholarPubMed
Carlson, SA & Werkman, SH (1996) A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months. Lipids 31, 85–90.CrossRefGoogle ScholarPubMed
Colombo, J (1997) Individual differences in infant cognition: methods, measures and models. In Developing Brain and Behaviour: The Role of Infant Formula, pp. 339–385 [Dobbing, J, editor]. London: Academic Press.CrossRefGoogle Scholar
Cunnane, SC (2000) The conditional nature of the dietary needs for polyunsaturates: a proposal to reclassify 'essential fatty acids' as 'conditionally-indispensable' or 'conditionally-dispensable' fatty acids. British Journal of Nutrition 84, 803–812.CrossRefGoogle ScholarPubMed
Damasio, A (1994) Descartes Error: Emotion, Reason and the Human Brain. New York: Avon Books.Google Scholar
Delion, S, Chalon, S, Guillotaeu, D, Besnard, J-C, & Durand, G (1996) α-Linolenic acid deficiency alters age-related changes of dopaminergic and serotonergic neurotransmission in the rat frontal cortex. Journal of Neurochemistry 66, 1582–1591.CrossRefGoogle Scholar
Delion, S, Chalon, S, Herault, J, Guilloteau, D, Besnard, JC & Durand, G (1994) Chronic α-linolenic acid deficiency alters dopaminergic and serotonergic neurotransmission in rats. Journal of Nutrition 124, 2466–2476.Google Scholar
Diamond, A, Prevor, MB, Callender, G & Druin, DP (1997) Prefrontal cortex cognitive deficits in children treated early and continuously for PKU. Monographs of the Society for Research in Child Development 62, 1–208.CrossRefGoogle ScholarPubMed
Everitt, BJ & Robbins, TW (1997) Central cholinergic systems and cognition. Annual Review of Psychology 48, 649–684.CrossRefGoogle ScholarPubMed
Fagan, JF (1990) The paired-comparison paradigm and infant intelligence. Annals of the New York Academy of Sciences 608, 337–364.CrossRefGoogle ScholarPubMed
Fernstrom, J (2000) Can nutrient supplements modify brain function? American Journal of Clinical Nutrition 71, Suppl., 1669S–1673S.Google ScholarPubMed
Francis, DD & Meaney, MJ (1999) Maternal care and the development of stress responses. Current Opinion in Neurobiology 9, 128–134.Google ScholarPubMed
Godfrey, KM & Barker, DJP (2000) Fetal nutrition and adult disease. American Journal of Clinical Nutrition 71, 1344S–1352S.CrossRefGoogle ScholarPubMed
Gottlieb, G (1998) Normally occurring environmental and behavioral influences on gene activity: from central dogma to probabilistic epigenesis. Psychological Review 105, 792–802.CrossRefGoogle ScholarPubMed
Gould, E, Reeves, AJ, Graziano, MSA & Gross, G (1999) Neurogenesis in the neocortex of adult primates. Science 286, 548–552.Google ScholarPubMed
Hayaishi, O (1991) Molecular mechanisms of sleep wake regulation: roles of prostaglandins D2 and E2. FASEB Journal 5, 2575–2581.CrossRefGoogle ScholarPubMed
Hibbeln, JR (1999) Long-chain polyunsaturated fatty acids in depression and related conditions. In Phospholipid Spectrum Disorder in Psychiatry, pp. 195–210 [Peet, M, Glen, I and Horrobin, DF, editors]. Carnforth, Lancs.: Marius Press.Google Scholar
Horrobin, DF (1999) The phospholipid concept of psychiatric disorders. In Phospholipid Spectrum Disorder in Psychiatry, pp. 3–20 [Peet, M, Glen, I and Horrobin, DF, editors]. Carnforth, Lancs.: Marius Press.Google Scholar
Innis, SM (2000) The role of dietary n-6 and n-3 fatty acids in the developing brain. Developmental Neuroscience 22, 474–480.CrossRefGoogle ScholarPubMed
Innis, SM & de la Presa Owens, S (1999) Docosahexenoic and arachidonic acid prevent a decrease in dopaminergic and serotonergic neurotransmitters in frontal cortex caused by a linoleic and α-linolenic deficient diet in formula-fed piglets. Journal of Nutrition 129, 2088–2093.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. Journal of Nutrition 131, 118–122.CrossRefGoogle ScholarPubMed
Jump, DB & Clarke, SD (1999) Regulation of gene expression by dietary fat. Annual Review of Nutrition 19, 63–90.CrossRefGoogle ScholarPubMed
Jumpsen, J & Clandinin, MT (1995) Brain Development: Relationship to Dietary Lipid and Lipid Metabolism. Champaign, IL: AOCS Press.Google Scholar
Kemperman, G & Gage, FH (1999) New nerve cells for the adult brain. Scientific American 280, 48–53.CrossRefGoogle Scholar
Kent, S, Bluthe, RM, Kelley, KW & Dantzer, R (1992) Sickness behaviour as a new target for drug development. Trends in Pharmacological Sciences 13, 24–28.CrossRefGoogle Scholar
Keshavan, MS & Hogarty, GE (1999) Brain maturational processes and delayed onset in schizophrenia. Development and Psychopathology 11, 525–543.CrossRefGoogle ScholarPubMed
Kinsella, JE, Broughton, KS & Whelan, JW (1990) Dietary unsaturated fatty acids: interactions and possible needs in relation to eicosanoid synthesis. Journal of Nutritional Biochemistry 1, 123–141.CrossRefGoogle ScholarPubMed
Klintsova, AY & Greenough, WT (1999) Synaptic plasticity in cortical systems. Current Opinion in Neurobiology 9, 203–208.CrossRefGoogle ScholarPubMed
Kolb, B, Forgie, M, Gibb, R, Gorny, G & Rowntree, S (1998) Age, experience and the changing brain. Neuroscience and Biobehavioral Reviews 22, 143–159.CrossRefGoogle ScholarPubMed
Lauder, JM (1993) Neurotransmitters as growth regulatory signals: Role of receptors and second messengers. Trends in Neurosciences 16, 233–240.CrossRefGoogle ScholarPubMed
Lauritzen, L, Hansen, HS, Jørgensen, MH & Michaelsen, KF (2001) The essentiality of long chain n-3 fatty acids in relation to development and function of the brain and retina. Progress in Lipid Research 40, 1–94.Google ScholarPubMed
Levitt, P, Harvey, JA, Friedman, E, Simansky, K & Murphy, EH (1997) New evidence for neurotransmitter influences on brain development. Trends in Neurosciences 20, 269–274.CrossRefGoogle ScholarPubMed
Lucas, A, Stafford, M, Morley, R, Abbott, R, Stephenson, T, MacFadyen, U, Elias-Jones, A & Clements, H (1999) Efficacy and safety of long-chain polyunsaturated fatty acid supplementation of infant-formula milk: a randomised trial. Lancet 354, 1948–1954.CrossRefGoogle ScholarPubMed
McEwen, BS, de Leon, MJ, Lupien, S & Meaney, MJ (1999) Corticosteroids, the aging brain and cognition. Trends in Endocrinology and Metabolism 10, 92–96.CrossRefGoogle ScholarPubMed
Martinez, M (1996) Docosahexaenoic acid therapy in docosahexaenoic acid-deficient patients with disorders of peroxisomal biogenesis. Lipids 31, S145–S152.CrossRefGoogle ScholarPubMed
Mills, DE & Huang, Y-S (1992) Metabolism of n-6 and n-3 polyunsaturated fatty acids in normotensive and hypertensive rats. In Essential Fatty Acids and Eicosanoids, pp. 345–348 [Sinclair, A and Gibson, R, editors]. Champaign, IL: AOCS.Google Scholar
Murphy, BL, Arnsten, AFT, Goldman-Rakic, PS & Roth, RH (1996) Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys. Proceedings of the National Academy of Sciences USA 93, 1325–1329.CrossRefGoogle ScholarPubMed
Nowakowski, RS & Hayes, NL (1999) CNS development: An overview. Development and Psychopathology 11, 395–417.CrossRefGoogle ScholarPubMed
Osterheld-Haas, MC & Hornung, JP (1996) Laminar development of the mouse barrel cortex: Effects of neurotoxins against monoamines. Experimental Brain Research 110, 183–195.CrossRefGoogle ScholarPubMed
Pollitt, E (2001) The developmental and probabilistic nature of the functional consequences of iron-deficiency anemia in children. Journal of Nutrition 131, 669S–675S.CrossRefGoogle ScholarPubMed
Quartz, SR & Sejnowski, TJ (1997) The neural basis of cognitive development: a constructivist manifesto. Behavioral and Brain Science 20, 537–596.CrossRefGoogle ScholarPubMed
Reisbick, S & Neuringer, M (1997) Omega-3 fatty acid deficiency and behavior: a critical review and future directions for research. In Handbook of Essential Fatty Acid Biology: Biochemistry, Physiology and Behavioral Neurobiology, pp. 397–426 [Yehuda, S and Mostofsky, DI, editors]. Totowa, NJ: Humana Press.CrossRefGoogle Scholar
Reisbick, S, Neuringer, M, Gohl, E, Wald, R & Anderson, GJ (1997) Visual attention in infant monkeys: effects of dietary fatty acids and age. Developmental Psychology 33, 387–395.CrossRefGoogle ScholarPubMed
Rodier, PM (1980) Chronology of neuron development: animal studies and their clinical implications. Developmental Medicine and Child Neurology 22, 525–545.CrossRefGoogle ScholarPubMed
Roudbaraki, MM, Droulhault, R, Bacquarty, T & Vacher, P (1996) Arachidonic acid-induced hormone release in somatotropes: involvement of calcium. Neuroendocrinology 63, 244–256.CrossRefGoogle ScholarPubMed
Sagvolden, T (2000) Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention deficit/hyperactivity disorder AD/HD. Neuroscience and Biobehavioral Reviews 24, 31–39.CrossRefGoogle ScholarPubMed
Saugstad, LF (1998) Cerebral lateralisation and rate of maturation. International Journal of Psychophysiology 28, 37–62.CrossRefGoogle ScholarPubMed
Scott, DT, Janowsky, JS, Carroll, RE, Taylor, JA, Auestad, N & Montalto, M (1998) Formula supplementation with long-chain polyunsaturated fatty acids: are there developmental benefits? Pediatrics 102, E59.CrossRefGoogle ScholarPubMed
Shatz, C (1992) The developing brain. Scientific American 267, 61–67.CrossRefGoogle ScholarPubMed
Siesjö, BK & Katsura, K (1992) Ischemic brain damage: focus on lipids and lipid mediators. In Neurobiology of Essential Fatty Acids, pp. 41–44 [Bazan, NG, Murphy, MG and Toffano, G, editors]. New York: Plenum Press.CrossRefGoogle Scholar
Stevens, LJ, Zentall, SS, Abate, ML, Kuczek, T & Burgess, JR (1996) Omega-3 fatty acids in boys with behavior, learning and health problems. Physiology and Behavior 59, 915–920.CrossRefGoogle ScholarPubMed
Taylor, E (1999) Developmental neuropsychopathology of attention deficit and impulsiveness. Development and Psychopathology 11, 607–628.CrossRefGoogle ScholarPubMed
Wainwright, PE (1992) Do essential fatty acids play a role in brain and behavioral development? Neuroscience and Biobehavioral Reviews 16, 193–205.CrossRefGoogle ScholarPubMed
Wainwright, PE (1997) Essential fatty acids and behaviour: is there a role for the eicosanoids? In Handbook of Essential Fatty Acid Biology: Biochemistry, Physiology and Behavioral Neurobiology, pp. 299–341 [Yehuda, S and Mostofsky, DI, editors]. Totowa, NJ: Humana Press.CrossRefGoogle Scholar
Wainwright, PE, Bulman-Fleming, MB, Lévesque, S, Mutsaers, L & McCutcheon, D (1998 a) Saturated-fat diet during development alters dendritic growth in mouse brain. Nutritional Neuroscience 1, 49–58.CrossRefGoogle ScholarPubMed
Wainwright, PE, Huang, Y-S, Bulman-Fleming, B, Lévesque, S & McCutcheon, D (1994 a) The effects of dietary fatty acid composition combined with environmental enrichment on brain and behavior in mice. Behavioural Brain Research 60, 125–136.CrossRefGoogle ScholarPubMed
Wainwright, PE, Huang, Y-S, Coscina, DV, Lévesque, S & McCutcheon, D (1994 b) Brain and behavioral effects of dietary (n-3) deficiency in mice: A three generation study. Developmental Psychobiology 27, 467–487.CrossRefGoogle Scholar
Wainwright, PE, Xing, H-C, Girard, T, Parker, L & Ward, GR (1998 b) Effects of dietary n-3 deficiency on amphetamine-conditioned place preference and working memory in the Morris water-maze. Nutritional Neuroscience 4, 281–293.CrossRefGoogle Scholar
Wainwright, PE, Xing, H-C, Mutsaers, L, McCutcheon, D & Kyle, D (1997) Arachidonic acid offsets the effects on mouse brain and behavior of a diet with a low (n-6):(n-3) ratio and very high levels of docosahexaenoic acid. Journal of Nutrition 127, 184–193.CrossRefGoogle Scholar
Wainwright, PE, Xing, H-C, Ward, GR, Huang, Y-S, Bobik, E, Auestad, N & Montalto, M (1999) Water maze performance is unaffected in artificially reared rats fed diets supplemented with arachidonic acid and docosahexaenoic acid. Journal of Nutrition 129, 1079–1089.CrossRefGoogle ScholarPubMed
Waisbren, SE (1999) Developmental and neuropsychological outcome in children born to mothers with phenylketonuria. Mental Retardation and Developmental Disabilities Research Reviews 5, 125–131.3.0.CO;2-P>CrossRefGoogle Scholar
Ward, GR, Huang, Y-S, Bobik, E, Xing, H-C, Mutsaers, L, Auestad, N, Montalto, M & Wainwright, PE (1998) Long-chain polyunstaurated fatty acid levels in formulae influence deposition of docosahexaenoic acid and arachidonic acid in brain and red blood cells of artificially reared neonatal rats. Journal of Nutrition 128, 2473–2487.Google Scholar
Wauben, IPM & Wainwright, PE (1999) The influence of neonatal nutrition on behavioral development: A critical appraisal. Nutrition Reviews 57, 35–44.CrossRefGoogle ScholarPubMed
Werkman, SW & Carlson, SE (1996) A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until nine months. Lipids 31, 91–97.CrossRefGoogle ScholarPubMed
Willatts, P, Forsyth, JS, DiMondugno, MK, Varma, S & Colvin, M (1998) Effect of long-chain polyunsaturated fatty acids in infant formula on problem solving at 10 months of age. Lancet 352, 688–691.CrossRefGoogle ScholarPubMed
Zimmer, I, Hembert, S, Dward, G, Breton, P, Guilloteau, D, Besnard, J-C, & Chalon, S (1998) Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study. Neuroscience Letters 240, 177–181.CrossRefGoogle ScholarPubMed