Abstract
Differences in visual, auditory, and learning tasks have been reported for infants and animals given diets varying in ω-3 fatty acids, but the neurobiochemical basis for these changes is unclear. This study investigated the effect of feeding formula with 0.8% energy C18:2ω-6 + 0.05% C18:3ω-3 (low), or 8.3% C18:2ω-6 + 0.8% C18:3ω-3 (adequate), with and without 0.2% energy arachidonic acid (C20:4ω-6) and 0.16% docosahexanoic acid (C22:6ω-3), on monoaminergic neurotransmitters in different brain regions of piglets fed formula from birth to 18 d. The amount of C18:2ω-6 + C18:3ω-3 fed in formula had a significant effect on frontal cortex dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, serotonin, and 5-hydroxyindolacetic acid; striatum serotonin and inferior colliculus serotonin, resulting in lower concentrations in piglets fed the low compared with adequate C18:2ω-6 + C18:3ω-3 formula. Inclusion of arachidonic acid and docosahexanoic acid in the low, but not in the adequate, C18:2ω-6 + C18:3ω-3 formula resulted in increased concentrations of all monoamines in the frontal cortex, and in striatum and inferior colliculus serotonin. Feeding arachidonic acid and docosahexanoic acid in the formulas increased dopamine and 5-hydroxyindolacetic acid in superior and inferior colliculus, areas related to processing and integration of visual and auditory information. Higher dopamine and 5-hydroxyindolacetic acid were found in these regions even when arachidonic acid and docosahexanoic acid were added to the C18:2ω-6 + C18:3ω-3 adequate formula. This study suggests that functional changes among animals and infants fed diets varying in ω-6 and ω-3 fatty acids may involve altered neurotransmitter metabolism.
Similar content being viewed by others
Main
The ω-6 and ω-3 fatty acids AA (C20:4ω-6) and DHA (C22:6ω-3) are important components of membrane phospholipids in the brain (1) and can be synthesized in vivo from the dietary precursors, linoleic (C18:2ω-6) and linolenic (C18:3ω-3) acid, respectively (2). AA and DHA are also available in the diet in fats of animal origin, and are provided to the breast-fed infant in human milk in concentrations representing approximately 0.5–0.7% and 0.2–0.4% milk fatty acids, respectively (3, 4). It is well known that AA and DHA are accumulated in large amounts in the brain during perinatal brain growth (5, 6), and many animal studies have shown that diets very low in C18:2ω-6 and C18:3ω-3 reduce brain AA and DHA and learning behaviors (7). Changes related to C18:3ω-3 fatty acid deficiency include reduced DHA in brain and retina, altered electroretinograms, decreased looking and VEP acuity, and changes in behavior (learning) in some, but not all, studies (7–13). Recently, lower auditory evoked brain stem response was reported for offspring of rats fed fish oil (providing DHA) in gestation (14). Despite the well-described changes in membrane fatty acids, however, the mechanism by which dietary ω-6 and ω-3 fatty acids alter learning, visual, and auditory functions has not been established.
It is well known that plasma and red blood cell AA and DHA concentrations in infants fed formulas with no AA or DHA are lower than in breast-fed infants or infants fed formulas supplemented with the latter long-chain ω-6 and ω-3 fatty acids (15–21). This, however, may simply reflect the difference in dietary AA and DHA intake, and is not ipso facto evidence of reduced brain AA and DHA. Studies using stable isotopes have shown preterm and term infants can desaturate C18:2ω-6 and C18:3ω-3 to AA and DHA, respectively (22–24), and brain astrocytes can synthesize AA and DHA (25). However, it is not clear whether the rate of C18:3ω-3 conversion in liver or brain is sufficient to meet the needs of growing tissues for DHA (23). Autopsy data show lower DHA, but not AA, in brain of infants fed formula rather than those who were breast-fed (26, 27), as well as higher VEP and looking acuity. Higher scores in tests of neurodevelopment in infants fed formula with DHA than in infants fed formulas without DHA (16–18, 28) is consistent with a hypothesis that dietary DHA is important for optimal brain DHA assimilation. On the other hand, lower brain DHA may be explained by inadequate dietary C18:3ω-3, or high C18:2ω-6/C18:3ω-3 resulting in inhibition of C18:3ω-3 desaturation (29, 30). Thus, it remains unclear as to whether dietary DHA has a specific role in developing brain, or whether the discrepancies among studies are explained by differences in the formula C18:3ω-3, C18:2ω-6/C18:3ω-3 ratio, or other confounding variables (31).
Recent studies from this laboratory demonstrated reduced dopamine, serotonin, and norepinephrine in frontal cortex of piglets fed formula low in C18:2ω-6 and C18:3ω-3 (32). Furthermore, inclusion of 0.4% AA plus 0.3% DHA in the formula prevented the decrease in monoaminergic neurotransmitters that resulted from feeding with the low C18:2ω-6 and C18:3ω-3 formula for only 18 d from birth (32). Cognitive and behavioral processes involve many brain regions, including striatum, hypothalamus, and hippocampus, in addition to frontal cortex. Superior colliculus is considered essential for visual-motor integration, whereas inferior colliculus is a source of auditory and tactile localization cues and vocalization (33–36). The current article reports the effects of feeding piglets a formula with low C18:2ω-6 and C18:3ω-3 or C18:2ω-6 and C18:3ω-3 at similar concentrations to infant formula, and the effects of AA and DHA supplementation on monoaminergic neurotransmitters in hippocampus, striatum, hypothalamus, and inferior and superior colliculus of formula-fed piglets. Results for frontal cortex are included for comparison and demonstrate the region- and neurotransmitter-specific effects of the C18:2ω-6 plus C18:3ω-3 and AA plus DHA content of formula. AA was included with DHA in the supplemented formula to avoid problems of reduced AA that may result from supplementation with only DHA (15, 37).
METHODS
Animals and diets.
Newborn male piglets weighing >1 kg at birth and <12 h old were assigned to be fed one of four formula diets (n = 6/group) which differed only in the composition of the fat (Table 1). Two of the formulas were low in C18:2ω-6 and C18:3ω-3, providing about 0.8% energy C18:2ω-6 and 0.05% energy C18:3ω-3 (low C18:2ω-6 + C18:3ω-3); the other two formulas had 8.3% energy C18:2ω-6 and 0.8% energy C18:3ω-3 (C18:2ω-6 + C18:3ω-3 adequate). One of each of the low and adequate C18:2ω-6 + C18:3ω-3 formulas had 0.2% energy (0.4% total fatty acids) AA and 0.16% energy (0.3% fatty acids) DHA. The AA and DHA were from single cell oils and were included in the formula during preparation by Nestle Research Centre, Lausanne, Switzerland. Other details concerning the formulas and feeding have been reported (32). Littermates were not assigned to the same diet. The procedures involving the piglets were approved by the Animal Care Committee of the University of British Columbia and conformed to the guidelines of the Canadian Council on Animal Care.
Sample collection.
Piglets were anesthetized at 18 d of age (ketamin hydrochloride, 37.5 mg/kg, MTC Pharmaceuticals, Cambridge, Canada; and xylazine hydrochloride, 3.75 mg/kg, Bayvet Division, Chenango, Etobicoke, Canada), then killed by intracardiac injection of 200 mg/kg pentobarbital. The brain was rapidly removed and weighed, and the frontal cortex, hippocampus, striatum, superior colliculus, inferior colliculus, and hypothalamus were dissected and frozen in liquid nitrogen. All of the samples were stored at −80°C until analysis.
Biochemical analysis.
Frontal cortex (100 mg), hippocampus (40 mg), striatum (40 mg), hypothalamus (50 mg), superior colliculus (40 mg), and inferior colliculus (30 mg) were homogenized (Sonics Materials Inc, Danbury, CT, U.S.A.) in 760 μL of perchloric acid (0.1 mol/L) with 40 μL of 3,4-dihydroxybenzylamine (3 μg/mL) as an internal standard, then centrifuged at 172,381 ×g for 1 h at 4°C. The supernatant was then used for analysis of monoamine concentrations by high-pressure liquid chromatography, as described in detail (32).
Frontal cortex, hippocampus, and striatum lipids were extracted (38), then PC, PE, PI, and PS were separated by thin-layer chromatography, as recently described (31). The separated phospholipids were recovered, and their fatty acid components were separated, identified, and quantified by gas-liquid chromatography (39). Inadequate sample was available from sufficient individual piglets for phospholipid fatty acid analysis of hypothalamus and superior and inferior colliculus.
Statistical analyses.
Results were compared between the groups using two-way ANOVA with the level of C18:2ω-6 + C18:3ω-3 (low or adequate) and no addition or addition of AA and DHA as the main effects. Statistically significant differences among the four groups were then determined using Fisher's least significant difference only with ANOVA results with p < 0.05.
RESULTS
The effects of the amount of C18:2ω-6 + C18:3ω-3, and the inclusion of single cell oils with AA and DHA in the formulas on dopamine, serotonin, and norepinephrine, and their metabolites, in different regions of the piglet brain are shown in Table 2. The levels of neurotransmitter pathways are heterogeneous in different areas, and as demonstrated by the results, affected differently by dietary ω-6 and ω-3 fatty acids. The concentrations of dopamine and its metabolites DOPAC and HVA and of serotonin and its metabolite 5-HIAA were all significantly lower in frontal cortex of piglets fed the low C18:2ω-6 + C18:3ω-3 diet than in piglets fed the other three diets. In contrast, despite the much higher concentrations of dopamine, DOPAC, and HVA in striatum than frontal cortex, the amount of ω-6 and ω-3 fatty acids in the formula had no statistically significant effect on striatum dopamine or its metabolites. An interaction was found between the amount of C18:2ω-6 + C18:3ω-3 and the addition of AA + DHA on the concentrations of serotonin in the striatum. The individual group comparisons indicated that feeding AA + DHA decreased serotonin in the striatum of piglets fed the C18:2ω-6 + C18:3ω-3 adequate formula, but not in those fed the low C18:2ω-6 + C18:3ω-3 formula (Table 2). Concentrations of dopamine and 5-HIAA in both the inferior and superior colliculus were significantly higher in piglets fed the formulas with AA and DHA than in piglets fed the formulas without AA + DHA. The individual group comparisons showed that the concentrations of dopamine and 5-HIAA in the superior colliculus and 5-HIAA in the inferior colliculus were significantly increased when AA and DHA were added to either the formula with low C18:2ω-6 + C18:3ω-3 or with adequate C18:2ω-6 + C18:3ω-3. The concentrations of dopamine in the inferior colliculus was statistically significantly increased when AA + DHA was included in the formula with adequate C18:2ω-6 + C18:3ω-3, but the higher dopamine in the inferior colliculus of piglets fed the low C18:2ω-6 + C18:3ω-3 formula with versus without AA + DHA was not of statistical significance.
The major focus of this study was analysis of changes in monoaminergic neurotransmitters and their metabolites caused by including AA + DHA in formula with different amounts of C18:2ω-6 and C18:3ω-3. Sufficient tissue was available to separate and analyze PC, PE, PI, and PS only for frontal cortex, hippocampus, and striatum, for which the concentrations of AA and DHA are shown in Figure 1. These analyses show both phospholipid class and region-specific effects of the formula C18:2ω-6 + C18:3ω-3 and AA (C20:4ω-6) + DHA (C22:6ω-3) content. Inclusion of 0.4% AA and 0.3% DHA in the low C18:2ω-6 + C18:3ω-3 formula resulted in significantly higher frontal cortex AA in PC and PI and DHA in PC, PE, PS, and PI; higher hippocampus DHA in PC, PE, and PS; and higher striatum AA in PS. Inclusion of AA and DHA in the C18:2ω-6 and C18:3ω-3 adequate formula, on the other hand, had no significant effect on the frontal cortex AA, but resulted in lower AA in PC, PE, and PI in hippocampus, and higher AA in PS in striatum. Inclusion of AA + DHA in the formula with adequate C18:2ω-6 and C18:3ω-3 also increased DHA in PE and PI in frontal cortex, and increased AA in PS in striatum.
DISCUSSION
The results of this study establish that the dietary intake of ω-6 and ω-3 fatty acids during the first 18 d after birth can have marked and diverse effects on monoaminergic neurotransmitters in brain regions involved in learning, behavior, and the integration and transmission of visual and auditory information. The decreased concentrations of dopamine, serotonin, and norepinephrine in the frontal cortex of piglets given approximately 1% dietary energy C18:2ω-6 and 0.05% C18:3ω-3, and the prevention of this decrease by feeding 0.25% energy AA + 0.15% DHA, have recently been described (32).
Of particular significance, the studies in this report show that supplementation of the diet fed to piglets with AA and DHA at levels similar to those in human milk (3, 4) resulted in increased dopamine and 5-HIAA, the metabolite of serotonin, in the superior and inferior colliculus in the formula-fed piglet. In contrast to the other brain regions analyzed, supplementation of the formula with AA + DHA increased dopamine in both the superior and inferior colliculus of piglets fed a formula with C18:2ω-6 + C18:3ω-3 concentrations similar to those in current infant formulas in North America. Linolenic acid (C18:3ω-3) represented 1.5% of the formula fatty acids, about 0.8% energy, with a C18:2ω-6/C18:3ω-3 ratio of 10:1 in the formula with adequate C18:2ω-6 and C18:3ω-3. Thus, it is possible that higher intakes of C18:3ω-3, or a lower C18:2ω-6/C18:3ω-3, would have facilitated higher dopamine and 5-HIAA concentrations with no further effect of supplementation with AA and DHA. Insufficient superior and inferior colliculus was available for separation and analysis of phospholipid fatty acids. However, supplementation of the C18:2ω-6 + C18:3ω-3 adequate formula with AA + DHA either increased or had no effect on AA and DHA in striatum and frontal cortex phospholipids, but decreased AA in PC, PE, and PI and decreased DHA in PE and PS in hippocampus. These results show that potential diet-induced changes in membrane fatty acids in superior and inferior colliculus cannot be estimated from the diet-induced changes in other brain regions, but require specific analysis. The demonstration that the effects of dietary ω-6 and ω-3 fatty acids is heterogeneous among different brain regions has been noted by others (40). Possible explanations include the stage of development in different regions when the dietary treatment was imposed, the relative proportions of myelin and nonmyelin membranes in the different regions, or potentially regional differences in AA and DHA synthesis, or membrane phospholipid synthesis and turnover. However, it needs to be considered that this study did involve analysis of neurotransmitters and fatty acids from multiple regions of the brain, raising the possibility of a type 1 error.
Visual function has been assessed in infants in relation to the amounts of DHA in milk and formula diets using behavioral measures of looking acuity and VEP, usually in response to counter-phase checkerboard or grating stimulation. Several studies have found lower VEP and looking acuity in preterm and term gestation infants fed standard formula than in infants fed formulas supplemented with DHA (16–18, 20) in similar amounts to that used in the studies here with piglets. Another study, however, has not found differences (15). The VEP represents part of the activity of the visual cortex in response to information passed by the retina and the geniculostriate path (33, 41), with the cortical visual threshold estimated by extrapolation of the measures to derive the acuity limit (41). Behavioral measures of looking acuity, on the other hand, involve transmission of the visual information, integration, and a motor response of the infant in orienting toward the grating stimuli (42). More recently, studies with young rats found that maternal dietary fish oil reduced auditory evoked brain stem responses in offspring (14), but 2.5% dietary DHA in the milk fed after birth increased auditory brain responses (S. de la Presa Owens, S.M. Innis, unpublished data). The superior colliculus, which was analyzed here, is a laminated mass of gray fibers in the mesencephalon that receives and is involved in the conveyance of visual information and is essential in visual motor integration, such as orienting behavior, and avoidance reaction, and in facilitating shifts in gaze (33, 34, 36). The inferior colliculus, on the other hand, is involved in processing of auditory information and visual and tactile localization cues (33, 35). Furthermore, monoamines are known to be involved in both visual and auditory pathways (43–45). The demonstration in our study that supplementing formula with AA + DHA increased superior and inferior colliculus dopamine and 5-HIAA suggests differences in visual and auditory responses, and behavioral tests of learning that involve integration of visual cues in infants and animals fed diets varying in ω-3 fatty acids (9–12, 16–18, 20, 28, 46) may involve changes in dopamine or serotonin metabolism.
Inasmuch as our studies involved supplementation with both AA + DHA, it is not possible to conclude a specific role of DHA in monoamine metabolism. However, lower dopamine and serotonin receptor binding, and lower dopamine concentrations in frontal cortex (47, 48) and reduced dopamine in synaptic vesicles after a learning task (49, 50) have been reported for second-generation rats fed a C18:3ω-3 fatty acid–deficient diet. Thus, information is available to suggest dietary ω-3 fatty acids may alter brain monoamine metabolism at multiple levels, possibly involving synthesis, receptor-mediated neurotransmitter release and uptake, and vesicle storage.
In summary, this study has shown that the amount of C18:2ω-6 + C18:3ω-3, and inclusion of small amounts of AA and DHA, in formula fed to neonatal piglets for as little as 18 d from birth had diverse and region-specific effects on monoaminergic neurotransmitters and phospholipid fatty acids. It seems possible that the functional changes associated with dietary ω-6 or ω-3 fatty acid deprivation or supplementation are likely to be the consequence of altered neurotransmitter metabolism. The marked decrease in dopamine, serotonin, and norepinephrine after dietary C18:2ω-6 and ω-3 fatty acid restriction strongly argues against early nutrition without adequate provision of these fatty acids in the parenteral or enteral diet. The increase in dopamine and 5-HIAA in superior and inferior colliculus of piglets fed formula with low C18:2ω-6 + C18:3ω-3 or with C18:2ω-6 + C18:3ω-3 concentrations typical of infant formula suggests dietary AA or DHA may have a specific role in dopamine and serotonin metabolism in areas involved in transmission of visual and auditory information. Whether changes in dopamine or serotonin metabolism are involved in the changes in visual or auditory function, or performance in developmental tests found in some studies with infants and animals fed ω-3 fatty acid–modified diets, remains to be determined.
Abbreviations
- AA:
-
arachidonic acid
- DHA:
-
docosahexanoic acid
- DOPAC:
-
3,4-dihydroxyphenylacetico
- HVA:
-
homovanillic acid
- 5-HIAA:
-
5-hydroxyindolacetic acid
- PC:
-
phosphatidylcholine
- PE:
-
phosphatidylethanolamine
- PS:
-
phosphatidylserine
- PI:
-
phosphatidylinositol
- VEP:
-
visual evoked potential
References
Sastry PS 1985 Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24: 69–176
Sprecher H, Luthria DL, Mohammed BS, Baykousheva SP 1995 Reevaluation of the pathways for the biosynthesis of polyunsaturated fatty acids. J Lipid Res 36: 2471–2477
Innis SM, King DJ 1999 Trans fatty acids in human milk are inversely associated with levels of essential all-cis ω-6 and ω-3 fatty acids, and determine trans, but not ω-6 and ω-3 fatty acids in plasma of breast-fed infants. Am J Clin Nutr 70: 383–390
Jensen RG 1989 The Lipids of Human Milk. CRC Press, Boca Raton, FL, pp 1–213
Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW 1980 Intrauterine fatty acid accretion rates in human brain: implications for fatty acid requirements. Early Human Dev 4: 121–129
Clandinin MT, Chappell JE, Leong S, Heim T, Swyer PR, Chance GW 1980 Extrauterine fatty acid accretion in infant brain: implications for fatty acid requirements. Early Human Dev 4: 131–138
Innis SM 1991 Essential fatty acids in growth and development. Prog Lipid Res 30: 39–103
Benolken RM, Anderson RE, Wheeler IG 1973 Membrane fatty acids associated with the electrical response in visual excitation. Science 182: 1253–1254
Bourre JM, Francois M, Youyou A, Dumont O, Piciotti M, Pascal G, Durand G 1989 The effects of dietary α-linolenic acid on the composition of nerve membranes, enzyme activity, amplitude of electrophysiological parameter resistance to poisons and performance of learning tasks in rats. J Nutr 119: 1880–1892
Lamptey MS, Walker BL 1976 A possible role for dietary linolenic acid in the development of the young rat. J Nutr 106: 86–93
Neuringer M, Connor WE, Lin DS, Barstad L, Luck S 1986 Biochemical and functional effects of prenatal and postnatal ω-3 deficiency on retina and brain in rhesus monkeys. Proc Natl Acad Sci USA 83: 4021–4025
Yamamoto N, Hashimoto A, Takemoto Y, Okuyama H, Nomura M, Kitajima R, Togashi T, Tamai Y 1988 Effect of dietary α-linolenate/linoleate balance on lipid composition and learning ability in rats. II. Discrimination process, extinction process, and glycolipid composition. J Lipid Res 29: 1013–1021
Wainwright PE, Ward GR 1997 Early nutrition and behaviour: a conceptual framework for critical analysis of research. In: Developing Brain and Behaviour: The Role of Lipids in Infant Formula. Academic Press, San Diego, CA, pp 388–425
Saste MD, Carver JD, Stockard JE, Benford VJ, Chen LT, Phelps CP 1998 Maternal diet fatty acid composition affects neurodevelopment in rat pup. J Nutr 128: 740–743
Auestad N, Montalto MB, Hall RT, Fitzgerald KM, Wheeler RE, Connor WE, Neuringer M, Connor SE, Hartmann EE 1997 Visual acuity, erythrocyte fatty acid composition, and growth in term infants fed formulas with long chain polyunsaturated fatty acids for one year. Pediatr Res 4: 1–10
Birch EE, Hoffman DR, Uauy R, Birch DG, Prestidge C 1998 Visual acuity and the essentiality of docosahexaenoic acid and arachidonic acid in the diet of term infants. Ped Res 44: 201–209
Carlson SE, Ford AJ, Werkman SH, Peeples JM, Koo WWK 1996 Visual acuity and fatty acid status of term infants fed human milk and formulas with and without docosahexaenoate and arachidonate from egg yolk lecithin. Pediatr Res 39: 882–888
Carlson SE, Werkman SH, Rhodes PG, Tolley EA 1993 Visual acuity development in healthy preterm infants: effect of marine-oil supplementation. Am J Clin Nutr 58: 35–42
Innis SM, Akrabawi SS, Diersen-Schade DA, Dobson V, Guy DG 1997 Visual acuity and blood lipids in term infants fed human milk or formulae. Lipids 32: 63–72
Makrides M, Neumann M, Simmer K, Pater J, Gibson R 1995 Are long-chain polyunsaturated fatty acids essential nutrients in infancy?. Lancet 345: 1463–1468
Putnam JC, Carlson SE, Devoe PW, Barness JS 1982 The effects of variations in dietary fatty acids on the fatty acid composition of erythrocyte phosphatidylcholine and phosphatidylethanolamine in human infants. Am J Clin Nutr 36: 106–114
Carnielli VP, Wattimena DJ, Luijendijk IH, Boerlage A, Degenhost HJ, Sauer PJ 1996 The very low birthweight premature infant is capable of synthesizing arachidonic and docosahexaenoic acids from linolenic and linolenic acids. Pediatr Res 40: 169–174
Innis SM, Sprecher H, Hachey D, Anderson R, Edmond J 1999 Neonatal polyunsaturated fatty acid metabolism. Lipids 34: 139–149
Salem N Jr, Wegher B, Mena P, Uauy R 1996 Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants. Proc Natl Acad Sci USA 93: 49–54
Moore SA, Yoder E, Murphy S, Dutton GR, Spector AA 1991 Astrocytes, not neurons, produce docosahexaenoic acid and arachidonic acid. J Neurochem 6: 518–524
Farquharson J, Cockburn F, Patrick WA, Jamieson EC, Logan RW 1992 Infant cerebral cortex phospholipid fatty-acid composition and diet. Lancet 340: 810–813
Makrides M, Neumann MA, Byard RW, Simmer K, Gibson RA 1994 Fatty acid composition of brain, retina, and erythrocytes in breast- and formula-fed infants. Am J Clin Nutr 60: 189–194
Willatts P, Forsyth P, Forsyth JS, DiModugno MK, Varna S, Colvin M 1998 Effect of long-chain polyunsaturated fatty acids in formula on infant problem solving at 10 months of age. Lancet 352: 688–691
Arbuckle LD, MacKinnon MJ, Innis SM 1994 Formula 18: 2(ω-6) and 18:3(ω-3) content and ratio influence long-chain polyunsaturated fatty acids in developing piglet liver and central nervous tissue. J Nutr 124: 289–298
Hrboticky N, MacKinnon MJ, Puterman ML, Innis SM 1989 Effect of a linoleic acid infant formula feeding on brain synaptosomal lipid accretion and enzyme thermotropic behavior in the piglet. J Lipid Res 30: 1173–1184
Gore SM 1999 Statistical considerations in infant nutrition trials. Lipids 34: 185–197
de la Presa Owens S, Innis SM 1999 Docosahexaenoic and arachidonic acid prevent a decrease in dopaminergic and serotoninergic neurotransmitters in piglets frontal cortex caused by a linoleic and alpha linolenic acid deficient diet in formula-fed piglets. J Nutr 129: 2088–2094
Afifi AK, Bergman RA 1986 Basic Neuroscience. A Structural and Functional Approach, 2nd Ed. Usdrban & Schwarzenberg, Baltimore-Munich, pp 170–180
Goodale MA, Murison RCC 1987 The effects of lesions of the superior colliculus on locomotor orientation and the orienting reflex in the cat. Brain Res 88: 243–261
Huffman RF, Henson OW 1990 The descending auditory pathways and acousticomotor systems: connections with the inferior colliculus. Brain Res Rev 15: 295–323
Sahibzada N, Dear P, Redgrave P 1986 Movements resembling avoidance or orientation elicited by electrical stimulation of the superior colliculus in rats. J Neurosci 6: 723–733
Carlson SE, Cooke RJ, Werkman SH, Tolley EA 1996 First year growth of preterm infants fed standard compared to marine-oil ω-3 supplemented formula. Lipids 27: 901–907
Folch J, Lees M, Sloane-Stanley GHA 1957 A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226: 497–509
Innis SM, Dyer R, Nelson CM 1994 Evidence that palmitic acid is absorbed as sω- 2 monoacylglycerol from human milk by breast-fed infants. Lipids 29: 541–545
Favreliere S, Barrier L, Durand G, Chalon S, Tallineau C 1998 Chronic dietary ω-3 polyunsaturated fatty acids deficiency affects the fatty acid composition of plasmenylethanolamine and phosphatidylethanolamine differently in rat frontal cortex, striatum, and cerebellum. Lipids 33: 401–407
Norcia AM, Tyler CW 1985 Spatial frequency sweep VEP: visual acuity during the first year of life. Vision Res 25: 1399–1408
Dobson V 1993 Visual acuity testing in infants: from laboratory to clinic. In: Early Visual Development. Oxford University Press, Oxford, UK, pp 318–334
Antal A, Keri S, Bodis-Wollner J 1997 Dopamine D2 receptor blockade alters the primary and cognitive components of visual evoked potentials in the monkey, Macaca fascicularis. Neurosci Lett 232: 179–181
Basmak H, Yildirim N, Erdinc O, Ywdakul S, Ozdemir G 1999 Effect of levodopa therapy on visual evoked potentials and visual acuity in amblyopia. Ophthalmologica 213: 110–113
Bhargava VK, McKean CM 1977 Role of 5-hydroxytryptamine in the modulation of acoustic brainstem (far-field) potentials. Neuropharmacology 16: 447–449
Carlson SE, Werkman SH 1996 A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months. Lipids 31: 85–90
Delion S, Chalon S, Guilloteau D, Besnard J-C, Durand G 1996 Alpha-linolenic acid dietary deficiency alters age-related changes of dopaminergic and serotoninergic neurotransmission in the rat frontal cortex. J Neurochem 66: 1582–1591
Delion S, Chalon S, Herault J, Guilloteau D, Besnard JC, Durand G 1994 Chronic dietary α-linoleic acid deficiency alters dopaminergic and serotonergic neurotransmitters in rats. J Nutr 124: 2466–2476
Yoshida S, Yasuda A, Kawazato K, Sakai K, Shimada T, Takeshita Y, Yuasa S, Kobayashi T, Watanabe S, Okuyama H 1997 Synaptic vesicle ultrastructural changes in the rat hippocampus induced by a combination of α-linolenate deficiency and a learning task. J Neurochem 68: 1261–1268
Zimmer L, Hembert S, Dward G, Breton P, Guilloteau D, Besnard J-C, Chalon S 1998 Chronic ω-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study. Neurosci Lett 240: 177–181
Author information
Authors and Affiliations
Additional information
Supported by a grant from the Medical Research Council (MRC) of Canada.
Rights and permissions
About this article
Cite this article
de la Presa Owens, S., Innis, S. Diverse, Region-Specific Effects of Addition of Arachidonic and Docosahexanoic Acids to Formula with Low or Adequate Linoleic and α-Linolenic Acids on Piglet Brain Monoaminergic Neurotransmitters. Pediatr Res 48, 125–130 (2000). https://doi.org/10.1203/00006450-200007000-00022
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1203/00006450-200007000-00022
This article is cited by
-
The sociodemographic characteristics and dietary and blood plasma fatty acid profiles of elderly Saudi women with Alzheimer disease
Lipids in Health and Disease (2019)