A Decrease in Cell Size Accompanies a Loss of Docosahexaenoate in the Rat Hippocampus

Rats raised on n-3 essential fatty acid deficient diets demonstrate spatial memory deficits. To investigate neuroanatomical correlates of these deficits, morphological analysis of the hippocampus were carried out. Adult, female rats were raised for three generations on n-3 deficient or n-3 supplemented diets. Two n-3 deficient diets contained adequate linoleic acid (LA), or high linoleic acid (high LA), and two supplemented diets contained LA supplemented with alpha-linolenic acid (+LNA), or linoleic supplementation with alpha- linolenic and docosahexaenoic acids (+LNA/DHA). The total fatty acid composition of the hippocampus revealed a profound loss (90%) in docosahexaenoic acid (DHA) in the hippocampi of LA and high LA animals compared to those on +LNA and +LNA/DHA diets with a reciprocal increase in docosapentaenoic acid (DPAn-6) in all phospholipid species. The volume, density; total number, and cell body size of neurons in CA1-3, granular and hilar layers of the hippocampus were measured at septal and temporal locations using unbiased stereology. No differences were detected in any of these measures except for in cell body size; CA1 pyramidal neurons in the LA group were significantly (p < 0.04) smaller than neurons in the +LNA/DHA group at the septal location.

[1]  N. Salem,et al.  Reversal of docosahexaenoic acid deficiency in the rat brain, retina, liver, and serum. , 2001, Journal of lipid research.

[2]  B. Slotnick,et al.  Olfactory discrimination deficits in n−3 fatty acid-deficient rats , 2001, Physiology & Behavior.

[3]  N. Salem,et al.  Behavioral Deficits Associated with Dietary Induction of Decreased Brain Docosahexaenoic Acid Concentration , 2000, Journal of neurochemistry.

[4]  Wendy A Suzuki,et al.  The hippocampus and memory: a comparative and ethological perspective , 2000, Current Opinion in Neurobiology.

[5]  Hee-Yong Kim,et al.  Inhibition of Neuronal Apoptosis by Docosahexaenoic Acid (22:6n-3) , 2000, The Journal of Biological Chemistry.

[6]  P. Gean,et al.  Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus , 2000, Synapse.

[7]  L. Acsády,et al.  Nerve growth factor but not neurotrophin-3 is synthesized by hippocampal GABAergic neurons that project to the medial septum , 2000, Neuroscience.

[8]  A. Nitta,et al.  Dietary n-3 fatty acid deficiency decreases nerve growth factor content in rat hippocampus , 2000, Neuroscience Letters.

[9]  D. Guilloteau,et al.  Chronic n-3 polyunsaturated fatty acid deficiency alters dopamine vesicle density in the rat frontal cortex , 2000, Neuroscience Letters.

[10]  N. Matsuki,et al.  Bidirectional actions of docosahexaenoic acid on hippocampal neurotransmissions in vivo , 2000, Brain Research.

[11]  Paul E. Gilbert,et al.  Testing neural network models of memory with behavioral experiments , 2000, Current Opinion in Neurobiology.

[12]  J. Bourre,et al.  Specific phospholipid fatty acid composition of brain regions in mice. Effects of n-3 polyunsaturated fatty acid deficiency and phospholipid supplementation. , 2000, Journal of lipid research.

[13]  Robert E. Hampson,et al.  Distribution of spatial and nonspatial information in dorsal hippocampus , 1999, Nature.

[14]  J. Farquharson,et al.  Infant cerebellar gray and white matter fatty acids in relation to age and diet , 1999, Lipids.

[15]  H. Eichenbaum.  The hippocampus and mechanisms of declarative memory , 1999, Behavioural Brain Research.

[16]  M. Lynch,et al.  Age-related changes in synaptic function: analysis of the effect of dietary supplementation with ω-3 fatty acids , 1999, Neuroscience.

[17]  K. Sugioka,et al.  Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats , 1999, Neuroscience.

[18]  F. Ödberg,et al.  A stereotaxic atlas of the forebrain of the bank vole (Clethrionomys glareolus) , 1999, Brain Research Bulletin.

[19]  D. Price,et al.  Evidence that nerve growth factor influences recent memory through structural changes in septohippocampal cholinergic neurons , 1999, The Journal of comparative neurology.

[20]  D. Sengelaub,et al.  Prenatal Gonadal Steroids Affect Adult Spatial Behavior, CA1 and CA3 Pyramidal Cell Morphology in Rats , 1998, Hormones and Behavior.

[21]  P. Gean,et al.  Cancellation of low-frequency stimulation-induced long-term depression by docosahexaenoic acid in the rat hippocampus , 1998, Neuroscience Letters.

[22]  E. Kishida,et al.  Distinctive inhibitory activity of docosahexaenoic acid against sphingosine-induced apoptosis. , 1998, Biochimica et biophysica acta.

[23]  B. Lejeune,et al.  Age-related changes in phospholipid fatty acid composition and monoaminergic neurotransmission in the hippocampus of rats fed a balanced or an n-3 polyunsaturated fatty acid-deficient diet. , 1997, Journal of lipid research.

[24]  H. Okuyama,et al.  Synaptic Vesicle Ultrastructural Changes in the Rat Hippocampus Induced by a Combination of α‐Linolenate Deficiency and a Learning Task , 1997, Journal of neurochemistry.

[25]  Y. Denkins,et al.  Retinal and brain accretion of long-chain polyunsaturated fatty acids in developing felines: the effects of corn oil-based maternal diets. , 1997, The American journal of clinical nutrition.

[26]  J. Bourre,et al.  Influence of a dietary alpha-linolenic acid deficiency on learning in the Morris water maze and on the effects of morphine. , 1996, European journal of pharmacology.

[27]  K. Mine,et al.  The chronic administration of docosahexaenoic acid reduces the spatial cognitive deficit following transient forebrain ischemia in rats , 1996, Neuroscience.

[28]  Andreas Wree,et al.  Local cerebral glucose utilization in perfusion-fixed rat brains , 1995, Journal of Neuroscience Methods.

[29]  R W Byard,et al.  Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. , 1994, The American journal of clinical nutrition.

[30]  N. Akaike,et al.  Facilitatory effect of docosahexaenoic acid on N‐methyl‐D‐aspartate response in pyramidal neurones of rat cerebral cortex. , 1994, The Journal of physiology.

[31]  R. Go´mez,et al.  Phosphatidylserine increases hippocampal synaptic efficacy , 1993, Brain Research Bulletin.

[32]  P. G. Reeves,et al.  AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. , 1993, The Journal of nutrition.

[33]  Mark J. West,et al.  New stereological methods for counting neurons , 1993, Neurobiology of Aging.

[34]  J. Farquharson,et al.  Infant cerebral cortex phospholipid fatty-acid composition and diet , 1992, The Lancet.

[35]  C B Cave,et al.  The hippocampus, memory, and space , 1991, Hippocampus.

[36]  D. Burns,et al.  Lipid activation of protein kinase C. , 1991, The Journal of biological chemistry.

[37]  C. Scali,et al.  Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. , 1991, European journal of pharmacology.

[38]  H. Gundersen,et al.  Unbiased stereological estimation of the number of neurons in the human hippocampus , 1990, The Journal of comparative neurology.

[39]  D. S. Lin,et al.  Dietary effects on brain fatty acid composition: the reversibility of n-3 fatty acid deficiency and turnover of docosahexaenoic acid in the brain, erythrocytes, and plasma of rhesus monkeys. , 1990, Journal of lipid research.

[40]  H J Gundersen,et al.  The efficiency of systematic sampling in stereology and its prediction * , 1987, Journal of microscopy.

[41]  Y. Nishizuka.  The role of protein kinase C in cell surface signal transduction and tumour promotion , 1984, Nature.

[42]  S. Carlson,et al.  The effect of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. , 1982, The American journal of clinical nutrition.

[43]  H. Kretschmann,et al.  Different volume changes of cerebral cortex and white matter during histological preparation. , 1982, Microscopica acta.

[44]  J. Puskin,et al.  Preparation and spectroscopic characterization of molecular species of brain phosphatidylserines. , 1980, Chemistry and physics of lipids.

[45]  W. Hoss,et al.  Separation of brain phosphatidylserines according to degree of unsaturation by thin-layer chromatography. , 1976, Analytical biochemistry.

[46]  J. O'brien,et al.  Fatty acid and fatty aldehyde composition of the major brain lipids in normal human gray matter, white matter, and myelin. , 1965, Journal of lipid research.

[47]  W. R. Morrison,et al.  PREPARATION OF FATTY ACID METHYL ESTERS AND DIMETHYLACETALS FROM LIPIDS WITH BORON FLUORIDE--METHANOL. , 1964, Journal of lipid research.

[48]  J. Folch,et al.  Preparation of lipide extracts from brain tissue. , 1951, The Journal of biological chemistry.

[49]  R. Hampson,et al.  Anatomic model of hippocampal encoding of spatial information , 1999, Hippocampus.

[50]  M. Lynch,et al.  Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids. , 1999, Neuroscience.

[51]  M. Moser,et al.  Functional differentiation in the hippocampus , 1998, Hippocampus.

[52]  P. Wainwright,et al.  Effects of Dietary n-3 Fatty Acid Deficiency on Morris Water-Maze Performance and Amphetamine-Induced Conditioned Place Preference in Rats. , 1998, Nutritional neuroscience.

[53]  P. Andersen,et al.  Spatial training in a complex environment and isolation alter the spine distribution differently in rat CA1 pyramidal cells. , 1997, The Journal of comparative neurology.

[54]  W. Connor,et al.  The effects of n-3 fatty acid deficiency and repletion upon the fatty acid composition and function of the brain and retina. , 1988, Progress in clinical and biological research.

[55]  B. Holub,et al.  Chapter 8 Chromatographic Analysis of Phosphoinositides and their Breakdown Products in Activated Blood Platelets/Neutrophils , 1987 .

[56]  Nicolas G. Bazan,et al.  Docosahexaenoic acid metabolism and inherited retinal degenerations. , 1987, Progress in clinical and biological research.

[57]  Hee-Yong Kim,et al.  CHAPTER 15 – DOCOSAHEXAENOIC ACID: MEMBRANE FUNCTION AND METABOLISM , 1986 .

[58]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[59]  M. Crawford,et al.  Nutritional influences in the evolution of mammalian brain. In: lipids, malnutrition & the developing brain. , 1971, Ciba Foundation symposium.