Brain and behavioral effects of dietary n‐3 deficiency in mice: A three generational study

Wainwright, P.E.; Huang, Y. S.; Coscina, Donald V.; Lévesque, Sylvie; McCutcheon, D.

doi:10.1002/dev.420270705

Cited by 77 publications

(36 citation statements)

References 56 publications

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“…Deprivation in a single generation did not alter locomotor activity (68), agreeing with our results. N-3 PUFA deprivation initiated during pregnancy and accompanied by excess dietary LA did not increase depression scores in mice in one study (67), nor did three consecutive generations of deprivation in another study (64). We found a significant difference and large effect size on the Porsolt forced-swim test for depression.…”

Section: Discussionmentioning

confidence: 50%

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One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats

DeMar

Bell

et al. 2006

Journal of Lipid Research

225

157

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Male rat pups at weaning (21 days of age) were subjected to a diet deficient or adequate in n-3 polyunsaturated fatty acids (n-3 PUFAs) for 15 weeks. Performance on tests of locomotor activity, depression, and aggression was measured in that order during the ensuing 3 weeks, after which brain lipid composition was determined. In the n-3 PUFA-deprived rats, compared with n-3 PUFA-adequate rats, docosahexaenoic acid (22:6n-3) in brain phospholipid was reduced by 36% and docosapentaenoic acid (22:5n-6) was elevated by 90%, whereas brain phospholipid concentrations were unchanged. N-3 PUFA-deprived rats had a significantly increased (P 5 0.03) score on the Porsolt forcedswim test for depression, and increased blocking time (P 5 0.03) and blocking number (P 5 0.04) scores (uncorrected for multiple comparisons) on the isolation-induced residentintruder test for aggression. Large effect sizes (d . 0.8) were found on the depression score and on the blocking time score of the aggression test. Scores on the open-field test for locomotor activity did not differ significantly between groups, and had only small to medium effect sizes. This single-generational n-3 PUFA-deprived rat model, which demonstrated significant changes in brain lipid composition and in test scores for depression and aggression, may be useful for elucidating the contribution of disturbed brain PUFA metabolism to human depression, aggression, and bipolar disorder.-DeMar, J. C., Jr., K. Ma, J. M. Bell, M. Igarashi, D. Greenstein, and S. I. Rapoport. One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats.

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Section: Discussionmentioning

confidence: 50%

“…Locomotor activity was increased in adult mice deprived of n-3 PUFAs over several generations (64), and in adult rats and mice whose mothers were deprived at conception or during gestation (65)(66)(67). Deprivation in a single generation did not alter locomotor activity (68), agreeing with our results.…”

Section: Discussionmentioning

confidence: 99%

One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats

DeMar

Bell

et al. 2006

Journal of Lipid Research

225

157

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“…At PND 22, there were highly significant differences in the amounts of n-3 and n-6 brain FAs between the transgenic-fed and wildtype-fed treatment groups; however, the percentage of reduction in DHA and total n-3 FA content in the control group was only 40% and 38%, respectively. Previous rodent studies with significant differences in Morris Water Maze test performance had reductions in brain n-3 FA composition (DHA and total n-3 FA content) Ͼ80% (9,32,33). Researchers using rodents with less extreme n-3 PUFA reductions (Յ60%), as was the case in this study, have generally shown fewer statistically significant differences between treatment groups (10,34).…”

Section: Discussionmentioning

confidence: 75%

Neonatal Growth Rate and Development of Mice Raised on Milk Transgenically Enriched With Omega-3 Fatty Acids

2007

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ABSTRACT:The n-3 polyunsaturated fatty acid (PUFA) status of the neonatal brain has been associated with cognitive capability in mice. Previously, transgenic mice expressing the Caenorhabditis elegans (C. elegans) n-3 fatty acid (FA) desaturase gene under the control of a lactation-induced mammary gland promoter were found to produce milk containing significantly elevated levels of ␣-linolenic (ALA) and eicosapentaenoic (EPA) acid. In this study, the preweaning growth rate and development of mouse pups consuming elevated n-3 PUFA milk produced by transgenic dams were evaluated using the Wahlsten observational test battery and the object novelty preference test. Brains were collected at weaning and analyzed for FA composition. Pups nursed on transgenic dams had earlier eye opening, higher visual placement scores, and 1.6-fold more docosahexaenoic acid (DHA) in their brains compared with pups raised on wildtype dams. There was no significant effect of milk treatment (transgenic versus control) on other developmental parameters or novelty preference behavior. The pups consuming the elevated n-3 PUFA transgenic milk had slower preweaning growth rates such that pups reared on wildtype dams producing control milk were heavier than pups reared on transgenic dams producing high n-3 PUFA milk by postnatal day 18. This transgenic model enables the provision of a high n-3 PUFA lactational environment independent of maternal diet or gestational FA status. T he health benefits of n-3 polyunsaturated fatty acids (PUFAs) have been demonstrated for a variety of diseases and disorders (1-3). N-3 PUFAs have also been shown to play a role in brain development. Studies found a positive correlation between the amount of alpha linolenic acid (18:3n-3, ALA) supplied in infant formula and neurodevelopment scores at 1 y of age (4). Improved visual acuity and cognitive development were also observed in infants supplemented with dietary n-3 highly unsaturated fatty acids (FAs) [FAs with Ն20 carbon atoms and four or more double bonds (HUFAs)] (5). Other studies reported no effect of n-3 HUFA supplementation on cognition, motor development, or growth when compared with infants fed on nonsupplemented formula and breast-fed infants (6). Although there is dissent in the literature as to the exact extent to which n-3 HUFA supplementation influences brain development, the majority of studies suggested that there is a weak association between the amount of time that infants are breast-fed and their scores on performance tests (7).In addition to research conducted on human infants, numerous studies have used model species to investigate the effects of n-3 PUFAs on behavior and cognitive capability as recently reviewed by Fedorova and Salem (8). The most widely used approach for the study of the effects of n-3 PUFA on rodent behavior has been to induce dietary n-3 PUFA deficiency. The majority of such studies have reported behavioral testing scores with statistically significant deficits attributable to dietary n-3 FA restriction (7,9,10). Evidence...

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“…In the past, two-generation models have generally involved an extended feeding period for the dam, often extending back to weaning (10)(11)(12)(13)(14). It would greatly shorten the experiment if the controlled feeding could begin after conception, so that time-pregnant dams could be obtained commercially.…”

Section: Maternal Diet Experimentsmentioning

confidence: 99%

Effects of an n-3-deficient diet on brain, retina, and liver fatty acyl composition in artificially reared rats

Moriguchi

Lim

Greiner

et al. 2004

Journal of Lipid Research

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Rat pups born to dams fed a diet with 3.1% of total fatty acids as ␣ -linolenic acid (LNA) were fed, using an artificial rearing system, either an n-3-deficient (n-3-Def) or an n-3-adequate (n-3-Adq) diet. Both diets contained 17.1% linoleic acid, but the n-3-Adq diet also contained 3.1% LNA. The percentage of brain docosahexaenoic acid (DHA) continuously decreased (71%) with time over the 29 days of the experiment, with concomitant increases in docosapentaenoic acid (DPAn-6). In the retina, the percentage of DHA rose in the n-3-Adq group, with an apparent increased rate around the time of eye opening. However, there was a flat curve for the percentage of DHA in the n-3-Def group and a rising DPAn-6 with time. Liver DHA was highest at the time of birth in the n-3-Adq group but fell off somewhat over the course of 29 days. This decrease was more pronounced in the n-3-Def group, and the DPAn-6 rose considerably during the second half of the experiment. This method presents a first-generation model for n-3 deficiency that is more similar to the case of human nutrition than is the commonly employed two-generation model. -Moriguchi, T., S-Y. Lim, R.

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Brain and behavioral effects of dietary n‐3 deficiency in mice: A three generational study

Cited by 77 publications

References 56 publications

One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats

One generation of n-3 polyunsaturated fatty acid deprivation increases depression and aggression test scores in rats

Neonatal Growth Rate and Development of Mice Raised on Milk Transgenically Enriched With Omega-3 Fatty Acids

Effects of an n-3-deficient diet on brain, retina, and liver fatty acyl composition in artificially reared rats

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