Glenn R. Ward

Effects of Dietary n-3 Fatty Acid Deficiency on Morris Water-Maze Performance and Amphetamine-Induced Conditioned Place Preference in Rats.

In these studies we examined whether dietary n-3 fatty acid (FA) deficiency in adult male rats was associated with effects on performance in the Morris water-maze and with the development of a conditioned place preference to low (0.5 mg/kg) and high (2.0 mg/kg) doses of amphetamine. The male rats used in these studies had been raised for two generations on n-3 deficient diets, which produced an n-6: n-3 FA ratio in brain lipids three times that of animals fed an n-3 adequate diet. Although the two groups did not differ on learning the position of the hidden platform in the Morris water-maze, the n-3 deficient rats did show deficits on a subsequent working memory version of this task, and swam longer distances to reach a visible platform. There were no differences between the groups on the development of a conditioned place preference although, during the initial conditioning cycle, the increase in activity in response to the high dose of amphetamine was apparent only in the n-3 deficient group. These findings provide preliminary support for effects of n-3 FA deficiency on working memory, but not on motivational processes as measured by response to a drug reward.

Early Nutrition and Behavior: A Conceptual Framework for Critical Analysis of Research

Publisher Summary This chapter discusses a conceptual framework for a critical analysis of the research on early nutrition and behavior. Critical analysis in behavioral research is informed by the concept of validity, which indicates the range of inferences that can be supported by an experimental outcome. Construct validity, is concerned with the ability to generalize from the research operations used to measure cause and effect to the theoretical constructs they putatively represent. A distinction is made between concurrent and predictive validity, based on the objectives of the test. Concurrent validation is relevant to tests used in the diagnoses of existing states, whereas predictive validation is concerned with the prediction of future outcomes. Some studies report that premature infants fed formulas devoid of long-chain polyunsaturated fatty acids exhibit higher rod (but not cone) electro-retinogram (ERG) b-wave thresholds and lower amplitudes, and that those receiving formulas supplemented with DHA show responses similar to those of breast-fed controls. It is suggested that the research into n-3 fatty acids and visual function relies heavily on the studies done in humans; many of these findings were preceded by similar observations in other animal species.

Combined effects of moderate ethanol consumption and a low-protein diet during gestation on brain development in BALBc mice

We investigated whether or not moderate ethanol consumption during gestation would interact with the effects of a low-protein diet in affecting brain development in BALB/c mice. The independent variables included fetal body and brain weights and cross-sectional area in midsagittal sections of the corpus callosum (CC) and anterior commissure (CA). Pregnant animals were fed either ethanol 12% v/v or an isocaloric sucrose solution from days 5 to 19 of gestation, when fetal development was assessed. In addition, the animals were fed semisynthetic isocaloric diets containing either 8 or 20% casein. All animals were pair-fed to those in the group receiving ethanol and 20% casein; an additional control group was fed lab chow ad libitum. There was clearly an interactive effect of diet and ethanol consumption on blood alcohol concentrations: those in the low-protein group were significantly higher than in the normal-protein group. Similarly, the effect on body weight in the group receiving low protein plus ethanol was greater than the additive effect of either treatment alone, although this may have been due partly to differences in litter size. Brain weight in this group was also significantly less than in the other three groups, which did not differ from each other. Covariance analysis, adjusting brain weight for body weight, suggested a brain-sparing effect of low protein but not ethanol. Neither treatment affected the incidence of the CC being absent at midline. The low-protein treatment decreased the cross-sectional area of both the CC and CA; the effect on the CC was independent of brain weight. There was no effect of ethanol on either of those measures.

Effects of postnatal ethanol exposure on brain growth and lipid composition in n−3 fatty acid-deficient and-adequate rats

The artificial rearing model was used to investigate the effects of short-term exposure to ethanol on growth and fatty acid composition of forebrain (FB) and cerebellum (CB) during the brain growth spurt in either n−3 fatty acid-adequate (AD) or n−3 deficient (DEF) rat pups. On postnatal day 5, offspring of female rats that had been fed AD or DEF diets from day 5 of life were assigned to three groups: members of two groups were gastrostomized and artificially fed formulas appropriate for their maternal history, and the third group (suckled control) was fostered to lactating dams of a similar dietary history. Half of the artificially reared pups in each dietary condition were fed ethanol in their formula (7% vol/vol) in one-quarter of their daily feedings, while the others received maltose-dextrin substituted isocalorically for ethanol. Blood alcohol concentrations did not differ betwen the dietary groups. FB weight on postnatal day 9 was lower in ethanol-exposed offspring in both dietary conditions. Brain fatty acid composition reflected dietary history in that, compared with AD pups, DEF pups had lower percentages of docosahexaenoic acid, higher percentages of 22∶5n−6, and a higher n−6/n−3 fatty acid ratio. However, the effects of ethanol exposure were inconsistent, lowering the n−6/n−3 ratio in the phosphatidylethanolamine (PF) fraction in FB but not in CB, while increasing this ratio in the phosphatidylcholine (PC) fraction in FB of the DEF pups only. Thus, while ethanol had some effects on lipid composition, there was no difference between the dietary groups in their vulnerability to the effects of early short-term ethanol exposure on brain growth.

The effects of a marginal essential fatty acid diet in the early neonatal period on whole-body glucose tolerance in artificially reared rats

In infant nutrition, attention has focused on the role of essential fatty acids (EFA), linoleic and linolenic acids, in neural development and visual function. Little is known about how glucose homeostasis may be affected by a marginal EFA (mEFA) diet in early life. This study investigated the effects of a mEFA diet (2.5% linoleic acid, 0.06% linolenic acid) in the early neonatal period on whole-body glucose tolerance in early and adult life in rats that were artificially reared (AR). Male Long-Evans rat pups, reared artificially from postnatal days 5 to 18, were fed a mEFA or a control (CON) diet; a suckle control (SC) group was raised by foster dams. From weaning (day 18) until approximately 70 days of age, rats in the mEFA, CON and half of those in the SC groups were fed a high-fat diet. The remaining rats in the SC group were fed a standard AIN diet after weaning. Oral glucose tolerance tests (OGTT) were performed at days 18 and 46 of age. An intravenous glucose tolerance test (IVGTT) was performed at 70 days of age. The percentage of pancreatic cells staining positive for insulin was determined at 70 days of age. AR lead to impaired glucose tolerance in rats fed the mEFA and CON diets at day 18 compared with the SC group (p = 0.0014), but had no lasting effects on glucose homeostasis up to 70 days of age. A mEFA diet during early post-natal life did not significantly affect glucose tolerance in adulthood, although there was some evidence of altered insulin secretory patterns in this group at 70 days of age. The percentage of cells staining positive for insulin did not differ among groups. Glucose homeostasis seems to be robust to marginal fatty acid intake during the early post-natal period. Possible alterations in insulin secretion resulting from a mEFA diet deserve further study.