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Chronic dietary intake of α-linolenic acid does not replicate the effects of DHA on passive properties of entorhinal cortex neurons

  • Dany Arsenault (a1) (a2), Carl Julien (a1) (a2) and Frédéric Calon (a1) (a2)
Abstract

n-3 PUFA are receiving growing attention for their therapeutic potential in central nervous system (CNS) disorders. We have recently shown that long-term treatment with DHA alters the physiology of entorhinal cortex (EC) neurons. In the present study, we investigated by patch-clamp the effect of another major dietary n-3 PUFA, α-linolenic acid (LNA), on the intrinsic properties of EC neurons. Mice were chronically exposed to isoenergetic diets deficient in n-3 PUFA or enriched in either DHA or LNA on an equimolar basis. GC analyses revealed an increase in DHA (34 %) and a decrease in arachidonic acid (AA, − 23 %) in brain fatty acid concentrations after consumption of the DHA-enriched diet. Dietary intake of LNA similarly affected brain fatty acid profiles, but at a lower magnitude (DHA: 23 %, AA: − 13 %). Compared to the n-3 PUFA-deficient diet, consumption of DHA, but not LNA, induced membrane hyperpolarisation ( − 60 to − 70 mV), increased cellular capacitance (32 %) and spontaneous excitatory postsynaptic current frequency (50 %). We propose that the inefficiency of LNA to modulate cellular capacitance was related to its inability to increase the brain DHA:AA ratio over the threshold necessary to up-regulate syntaxin-3 (46 %) and translocate drebrin (40 % membrane:cytosol ratio). In summary, our present study shows that the increase in brain DHA content following chronic administration of LNA was not sufficient to alter the passive and synaptic properties of EC neurons, compared to direct dietary intake of DHA. These diverging results have important implications for the therapeutic use of n-3 PUFA in CNS disease, favouring the use of preformed DHA.

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Corresponding author
*Corresponding author: Dr F. Calon, fax +1 418 654 2761, email frederic.calon@pha.ulaval.ca
References
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1 Salem, N Jr (1989) Omega-3 fatty acids: molecular and biochemical aspects. In New Protective Roles for Selected Nutrients, pp. 109228 [Spiller, GA and Scala, J, editors]. New York, NY: Alan R. Liss.
2 Brenna, JT, Salem, N Jr, Sinclair, AJ, et al. (2009) Alpha-linolenic acid supplementation and conversion to n-3 long-chain polyunsaturated fatty acids in humans. Prostaglandins Leukot Essent Fatty Acids 80, 8591.
3 Umhau, JC, Zhou, W, Carson, RE, et al. (2009) Imaging incorporation of circulating docosahexaenoic acid into the human brain using positron emission tomography. J Lipid Res 50, 12591268.
4 Farquharson, J, Cockburn, F, Patrick, WA, et al. (1992) Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet 340, 810813.
5 Makrides, M, Neumann, MA, Byard, RW, et al. (1994) Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 60, 189194.
6 Moriguchi, T, Greiner, RS & Salem, N Jr (2000) Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration. J Neurochem 75, 25632573.
7 Calon, F, Lim, GP, Morihara, T, et al. (2005) Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer's disease. Eur J Neurosci 22, 617626.
8 Bousquet, M, Saint-Pierre, M, Julien, C, et al. (2008) Beneficial effects of dietary omega-3 polyunsaturated fatty acid on toxin-induced neuronal degeneration in an animal model of Parkinson's disease. FASEB J 22, 12131225.
9 Harris, WS (2008) The omega-3 index as a risk factor for coronary heart disease. Am J Clin Nutr 87, 1997S2002S.
10 Carrie, I, Smirnova, M, Clement, M, et al. (2002) Docosahexaenoic acid-rich phospholipid supplementation: effect on behavior, learning ability, and retinal function in control and n-3 polyunsaturated fatty acid deficient old mice. Nutr Neurosci 5, 4352.
11 Fedorova, I, Hussein, N, Baumann, MH, et al. (2009) An n-3 fatty acid deficiency impairs rat spatial learning in the Barnes maze. Behav Neurosci 123, 196205.
12 Kidd, PM (2007) Omega-3 DHA and EPA for cognition, behavior, and mood: clinical findings and structural-functional synergies with cell membrane phospholipids. Altern Med Rev 12, 207227.
13 Calon, F & Cole, G (2007) Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids 77, 287293.
14 Cole, GM, Ma, QL & Frautschy, SA (2009) Omega-3 fatty acids and dementia. Prostaglandins Leukot Essent Fatty Acids 81, 213221.
15 Cunnane, SC, Plourde, M, Pifferi, F, et al. (2009) Fish, docosahexaenoic acid and Alzheimer's disease. Prog Lipid Res 48, 239256.
16 Yurko-Mauro, K, McCarthy, D, Rom, D, et al. (2010) Beneficial effects of docosahexaenoic acid on cognition in age-related cognitive decline. Alzheimers Dement 6, 456464.
17 Bruno, MJ, Koeppe, RE 2nd & Andersen, OS (2007) Docosahexaenoic acid alters bilayer elastic properties. Proc Natl Acad Sci U S A 104, 96389643.
18 Wassall, SR & Stillwell, W (2009) Polyunsaturated fatty acid-cholesterol interactions: domain formation in membranes. Biochim Biophys Acta 1788, 2432.
19 Calon, F, Lim, GP, Yang, F, et al. (2004) Docosahexaenoic acid protects from dendritic pathology in an Alzheimer's disease mouse model. Neuron 43, 633645.
20 Akbar, M, Calderon, F, Wen, Z, et al. (2005) Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci U S A 102, 1085810863.
21 de Urquiza, AM, Liu, S, Sjoberg, M, et al. (2000) Docosahexaenoic acid, a ligand for the retinoid X receptor in mouse brain. Science 290, 21402144.
22 Ethier, I, Kagechika, H, Shudo, K, et al. (2004) Docosahexaenoic acid reduces haloperidol-induced dyskinesias in mice: involvement of Nur77 and retinoid receptors. Biol Psychiatry 56, 522526.
23 Calder, PC (2002) Dietary modification of inflammation with lipids. Proc Nutr Soc 61, 345358.
24 Boudrault, C, Bazinet, RP, Kang, JX, et al. (2011) Cyclooxygenase-2 and n-6 PUFA are lower and DHA is higher in the cortex of fat-1 mice. Neurochem Int 56, 585589.
25 Lalancette-Hébert, M, Julien, C, Cordeau, PJ, et al. (2011) Accumulation of dietary DHA in the brain attenuates acute immune response and development of post-ischemic neuronal damage. Stroke (In the Press).
26 Biou, V, Brinkhaus, H, Malenka, RC, et al. (2008) Interactions between drebrin and Ras regulate dendritic spine plasticity. Eur J Neurosci 27, 28472859.
27 Curtis, LB, Doneske, B, Liu, X, et al. (2008) Syntaxin 3b is a t-SNARE specific for ribbon synapses of the retina. J Comp Neurol 510, 550559.
28 Darios, F & Davletov, B (2006) Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3. Nature 440, 813817.
29 Cansev, M & Wurtman, RJ (2007) Chronic administration of docosahexaenoic acid or eicosapentaenoic acid, but not arachidonic acid, alone or in combination with uridine, increases brain phosphatide and synaptic protein levels in gerbils. Neuroscience 148, 421431.
30 Arsenault, D, Julien, C, Tremblay, C, et al. (2011) DHA improves cognition and prevents dysfunction of entorhinal cortex neurons in 3xTg-AD mice. PLoS One 6, e17397.
31 Salem, N Jr, Pawlosky, R, Wegher, B, et al. (1999) In vivo conversion of linoleic acid to arachidonic acid in human adults. Prostaglandins Leukot Essent Fatty Acids 60, 407410.
32 Mayes, C, Burdge, GC, Bingham, A, et al. (2006) Variation in [U-13C] alpha linolenic acid absorption, beta-oxidation and conversion to docosahexaenoic acid in the pre-term infant fed a DHA-enriched formula. Pediatr Res 59, 271275.
33 Plourde, M & Cunnane, SC (2007) Extremely limited synthesis of long chain polyunsaturates in adults: implications for their dietary essentiality and use as supplements. Appl Physiol Nutr Metab 32, 619634.
34 Burdge, GC & Calder, PC (2006) Dietary alpha-linolenic acid and health-related outcomes: a metabolic perspective. Nutr Res Rev 19, 2652.
35 Jenkins, DJ, Sievenpiper, JL, Pauly, D, et al. (2009) Are dietary recommendations for the use of fish oils sustainable? CMAJ 180, 633637.
36 Sewards, TV & Sewards, MA (2003) Input and output stations of the entorhinal cortex: superficial vs. deep layers or lateral vs. medial divisions? Brain Res Brain Res Rev 42, 243251.
37 Kumar, SS, Jin, X, Buckmaster, PS, et al. (2007) Recurrent circuits in layer II of medial entorhinal cortex in a model of temporal lobe epilepsy. J Neurosci 27, 12391246.
38 Bragin, DE, Sanderson, JL, Peterson, S, et al. (2009) Development of epileptiform excitability in the deep entorhinal cortex after status epilepticus. Eur J Neurosci 30, 611624.
39 Braak, H & Braak, E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82, 239259.
40 Gomez-Isla, T, Price, JL, McKeel, DW, et al. (1996) Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease. J Neurosci 16, 44914500.
41 Haroutunian, V, Purohit, DP, Perl, DP, et al. (1999) Neurofibrillary tangles in nondemented elderly subjects and mild Alzheimer disease. Arch Neurol 56, 713718.
42 Duyckaerts, C, Delatour, B & Potier, MC (2009) Classification and basic pathology of Alzheimer disease. Acta Neuropathol 118, 536.
43 Hogan, SA, O'Riordan, ED & O'Sullivan, M (2003) Microencapsulation and oxidative stability of spray-dried fish oil emulsions. J Microencapsul 20, 675688.
44 Kolanowski, W, Laufenberg, G & Kunz, B (2004) Fish oil stabilisation by microencapsulation with modified cellulose. Int J Food Sci Nutr 55, 333343.
45 Whelan, J & Rust, C (2006) Innovative dietary sources of n-3 fatty acids. Annu Rev Nutr 26, 75103.
46 Diau, GY, Hsieh, AT, Sarkadi-Nagy, EA, et al. (2005) The influence of long chain polyunsaturate supplementation on docosahexaenoic acid and arachidonic acid in baboon neonate central nervous system. BMC Med 3, 11.
47 Brenna, JT & Diau, GY (2007) The influence of dietary docosahexaenoic acid and arachidonic acid on central nervous system polyunsaturated fatty acid composition. Prostaglandins Leukot Essent Fatty Acids 77, 247250.
48 Dullemeijer, C, Zock, PL, Coronel, R, et al. (2008) Differences in fatty acid composition between cerebral brain lobes in juvenile pigs after fish oil feeding. Br J Nutr 100, 794800.
49 Hsieh, AT & Brenna, JT (2009) Dietary docosahexaenoic acid but not arachidonic acid influences central nervous system fatty acid status in baboon neonates. Prostaglandins Leukot Essent Fatty Acids 81, 105110.
50 Julien, C, Berthiaume, L, Hadj-Tahar, A, et al. (2006) Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys. Neurochem Int 48, 404414.
51 Folch, J, Lees, M & Sloane Stanley, GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497509.
52 Zhang, ZW & Arsenault, D (2005) Gain modulation by serotonin in pyramidal neurones of the rat prefrontal cortex. J Physiol 566, 379394.
53 Arsenault, D & Zhang, ZW (2006) Developmental remodelling of the lemniscal synapse in the ventral basal thalamus of the mouse. J Physiol 573, 121132.
54 Golowasch, J, Thomas, G, Taylor, AL, et al. (2009) Membrane capacitance measurements revisited: dependence of capacitance value on measurement method in nonisopotential neurons. J Neurophysiol 102, 21612175.
55 Bourre, JM, Francois, M, Youyou, A, et al. (1989) The effects of dietary alpha-linolenic acid on the composition of nerve membranes, enzymatic activity, amplitude of electrophysiological parameters, resistance to poisons and performance of learning tasks in rats. J Nutr 119, 18801892.
56 Salem, N Jr, Moriguchi, T, Greiner, RS, et al. (2001) Alterations in brain function after loss of docosahexaenoate due to dietary restriction of n-3 fatty acids. J Mol Neurosci 16, 299307, (discussion 317–221).
57 Green, KN, Martinez-Coria, H, Khashwji, H, et al. (2007) Dietary docosahexaenoic acid and docosapentaenoic acid ameliorate amyloid-beta and tau pathology via a mechanism involving presenilin 1 levels. J Neurosci 27, 43854395.
58 Julien, C, Tremblay, C, Phivilay, A, et al. (2010) High-fat diet aggravates amyloid-beta and tau pathologies in the 3xTg-AD mouse model. Neurobiol Aging 31, 15161531.
59 Gentet, LJ, Stuart, GJ & Clements, JD (2000) Direct measurement of specific membrane capacitance in neurons. Biophys J 79, 314320.
60 Faumont, S, Boulin, T, Hobert, O, et al. (2006) Developmental regulation of whole cell capacitance and membrane current in identified interneurons in C. elegans. J Neurophysiol 95, 36653673.
61 Robson, LG, Dyall, S, Sidloff, D, et al. (2008) Omega-3 polyunsaturated fatty acids increase the neurite outgrowth of rat sensory neurones throughout development and in aged animals. Neurobiol Aging 31, 678687.
62 Cao, D, Kevala, K, Kim, J, et al. (2009) Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. J Neurochem 111, 510521.
63 He, C, Qu, X, Cui, L, et al. (2009) Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid. Proc Natl Acad Sci U S A 106, 1137011375.
64 Shim, KS & Lubec, G (2002) Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome. Neurosci Lett 324, 209212.
65 Sekino, Y, Kojima, N & Shirao, T (2007) Role of actin cytoskeleton in dendritic spine morphogenesis. Neurochem Int 51, 92104.
66 Moolman, DL, Vitolo, OV, Vonsattel, JP, et al. (2004) Dendrite and dendritic spine alterations in Alzheimer models. J Neurocytol 33, 377387.
67 Ouellet, M, Emond, V, Chen, CT, et al. (2009) Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood–brain barrier: an in situ cerebral perfusion study. Neurochem Int 55, 476482.
68 Rapoport, SI, Rao, JS & Igarashi, M (2007) Brain metabolism of nutritionally essential polyunsaturated fatty acids depends on both the diet and the liver. Prostaglandins Leukot Essent Fatty Acids 77, 251261.
69 Mohrhauer, H & Holman, RT (1963) Alteration of the fatty acid composition of brain lipids by varying levels of dietary essential fatty acids. J Neurochem 10, 523530.
70 Galli, C, White, HB Jr & Paoletti, R (1971) Lipid alterations and their reversion in the central nervous system of growing rats deficient in essential fatty acids. Lipids 6, 378387.
71 Bourre, JM (1989) Nature, origin and role of fatty acids of the nervous system: an essential fatty acid, an alpha-linolenic acid, changing the structure and the cerebral function. Bull Acad Natl Med 173, 11371148, discussion 1148–1151.
72 Brenna, JT (2011) Animal studies of the functional consequences of suboptimal polyunsaturated fatty acid status during pregnancy, lactation and early post-natal life. Matern Child Nutr 7, Suppl. 2, 5979.
73 Abedin, L, Lien, EL, Vingrys, AJ, et al. (1999) The effects of dietary alpha-linolenic acid compared with docosahexaenoic acid on brain, retina, liver, and heart in the guinea pig. Lipids 34, 475482.
74 Youyou, A, Durand, G, Pascal, G, et al. (1986) Recovery of altered fatty acid composition induced by a diet devoid of n-3 fatty acids in myelin, synaptosomes, mitochondria, and microsomes of developing rat brain. J Neurochem 46, 224228.
75 Groeger, AL, Cipollina, C, Cole, MP, et al. (2011) Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids. Nat Chem Biol 6, 433441.
76 Wurtman, RJ, Cansev, M & Ulus, IH (2009) Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J Nutr Health Aging 13, 189197.
77 Sakamoto, T, Cansev, M & Wurtman, RJ (2007) Oral supplementation with docosahexaenoic acid and uridine-5′-monophosphate increases dendritic spine density in adult gerbil hippocampus. Brain Res 1182, 5059.
78 Susarla, BT, Seal, RP, Zelenaia, O, et al. (2004) Differential regulation of GLAST immunoreactivity and activity by protein kinase C: evidence for modification of amino and carboxyl termini. J Neurochem 91, 11511163.
79 Tilleux, S & Hermans, E (2008) Down-regulation of astrocytic GLAST by microglia-related inflammation is abrogated in dibutyryl cAMP-differentiated cultures. J Neurochem 105, 22242236.
80 Grintal, B, Champeil-Potokar, G, Lavialle, M, et al. (2009) Inhibition of astroglial glutamate transport by polyunsaturated fatty acids: evidence for a signalling role of docosahexaenoic acid. Neurochem Int 54, 535543.
81 Robinson, MB (2006) Acute regulation of sodium-dependent glutamate transporters: a focus on constitutive and regulated trafficking. Handb Exp Pharmacol 251275.
82 Chytrova, G, Ying, Z & Gomez-Pinilla, F (2010) Exercise contributes to the effects of DHA dietary supplementation by acting on membrane-related synaptic systems. Brain Res 1341, 3240.
83 Kojima, N, Hanamura, K, Yamazaki, H, et al. (2010) Genetic disruption of the alternative splicing of drebrin gene impairs context-dependent fear learning in adulthood. Neuroscience 165, 138150.
84 Toda, M, Shirao, T & Uyemura, K (1999) Suppression of an actin-binding protein, drebrin, by antisense transfection attenuates neurite outgrowth in neuroblastoma B104 cells. Brain Res Dev Brain Res 114, 193200.
85 Catalan, J, Moriguchi, T, Slotnick, B, et al. (2002) Cognitive deficits in docosahexaenoic acid-deficient rats. Behav Neurosci 116, 10221031.
86 Petursdottir, AL, Farr, SA, Morley, JE, et al. (2008) Effect of dietary n-3 polyunsaturated fatty acids on brain lipid fatty acid composition, learning ability, and memory of senescence-accelerated mouse. J Gerontol A Biol Sci Med Sci 63, 11531160.
87 Yurko-Mauro, K (2010) Cognitive and cardiovascular benefits of docosahexaenoic acid in aging and cognitive decline. Curr Alzheimer Res 7, 190196.
88 Cole, GM & Frautschy, SA (2010) DHA may prevent age-related dementia. J Nutr 140, 869874.
89 Fedorova, I, Alvheim, AR, Hussein, N, et al. (2009) Deficit in prepulse inhibition in mice caused by dietary n-3 fatty acid deficiency. Behav Neurosci 123, 12181225.
90 Lafourcade, M, Larrieu, T, Mato, S, et al. (2011) Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. Nat Neurosci 14, 345350.
91 Blondeau, N, Nguemeni, C, Debruyne, DN, et al. (2009) Subchronic alpha-linolenic acid treatment enhances brain plasticity and exerts an antidepressant effect: a versatile potential therapy for stroke. Neuropsychopharmacology 34, 25482559.
92 Xiao, Y & Li, X (1999) Polyunsaturated fatty acids modify mouse hippocampal neuronal excitability during excitotoxic or convulsant stimulation. Brain Res 846, 112121.
93 Young, C, Gean, PW, Chiou, LC, et al. (2000) Docosahexaenoic acid inhibits synaptic transmission and epileptiform activity in the rat hippocampus. Synapse 37, 9094.
94 Taha, AY, Huot, PS, Reza-Lopez, S, et al. (2008) Seizure resistance in fat-1 transgenic mice endogenously synthesizing high levels of omega-3 polyunsaturated fatty acids. J Neurochem 105, 380388.
95 Taha, AY, Burnham, WM & Auvin, S (2010) Polyunsaturated fatty acids and epilepsy. Epilepsia 51, 13481358.
96 Schlanger, S, Shinitzky, M & Yam, D (2002) Diet enriched with omega-3 fatty acids alleviates convulsion symptoms in epilepsy patients. Epilepsia 43, 103104.
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