Valerie J Benford

The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects

The important role that neural tissue fatty acid composition plays in neurodevelopment and various pathological states is increasingly recognized. However, there are limited data regarding the fatty acid composition of normal human brain at various ages. The purpose of this study was to describe human cerebral cortex fatty acid composition from ages 2 to 88 years. The relationship between cerebral cortex and erythrocyte fatty acid composition was also investigated. Samples of frontal cerebral cortex and of erythrocytes were obtained from 58 human subjects on whom autopsies were performed. The mean age of subjects was 40 +/- 29 years, with a range of 2 to 88 years. The fatty acid composition of tissues was determined, and linear regression models were used to describe the relationship between age and the fatty acid composition of cerebral cortex and erythrocytes. The data were bilinear, with changes occurring after the approximate age of 18 years. Therefore, the cohort was divided into subjects with ages < or =18 and >18 years. In the younger group, the polyunsaturated fatty acids generally decreased with age, with the exception of 22:6n3, which demonstrated a significant increase. The level of mono-unsaturated fatty acids, in contrast, generally increased to the age of 18 years. Several of the polyunsaturated fatty acids also decreased with age in the older cohort, particularly 20:4n6. The levels of 18:2n6, however, increased significantly with age in the older cohort. Among subjects < or =18 years of age, there was no significant relationship between cerebral cortex and erythrocyte fatty acid levels. In the older cohort, there was a significant relationship between brain and erythrocyte levels for several fatty acids, particularly 16:0. These data demonstrate that levels of cerebral cortex fatty acids change from early childhood through late adulthood, and indicate that the levels of several erythrocyte fatty acids may be useful in predicting brain fatty acid levels in adults.

Effect of Docosahexaenoic Acid Content of Maternal Diet on Auditory Brainstem Conduction Times in Rat Pups

Previous studies of dietary docosahexaenoic acid (DHA; 22:6n–3) effects on neurodevelopment have focused mainly on effects on the visual system; these studies may be confounded by effects on the retina rather than on neural pathways. Auditory brainstem conduction times (ABCTs) provide an alternate measure of central neural development. We conducted a dose-response study in which ABCTs were measured in pups whose dams were fed diets containing one of three levels of DHA (2, 4 or 6% of total fatty acids) from a single cell oil. Diets were fed during pregnancy and lactation, and pups were randomly cross-fostered on postnatal day 3 to minimize litter effects. ABCTs showed a dose-response effect, with higher levels of dietary DHA being associated with longer conduction times on postnatal day 31 (p < 0.05). Higher dietary DHA was reflected in pup cerebrums collected on postnatal days 3 and 31, and levels of arachidonic acid (AA, 20:4n–6) were inversely related to levels of DHA. This study demonstrated that the auditory brainstem response is sensitive for identifying effects of diet on neurodevelopment, and that supplementing the maternal diet with high levels of DHA may negatively impact development of the central auditory system of offspring.

The fatty acid composition of maternal diet affects the response to excitotoxic neural injury in neonatal rat pups.

Fatty acids and their derivatives play a role in the response to neural injury. The effects of prenatal and postnatal dietary fatty acid composition on excitotoxic neural injury were investigated in neonatal rat pups. Dams were fed during gestation and lactation a diet whose fat source was either corn oil or menhaden fish oil. On postnatal day 3, litters were culled to 10 per dam. On postnatal day 4, excitotoxic neural injury was induced by infusion of the glutamate analog N-methyl-DL-aspartate (NMA) into the left cerebral hemisphere. Three days later, pups were killed and brains were removed for histological and volume assessments. Levels of arachidonic acid were 2.3-fold higher in cerebrums of pups in the corn oil group than in the fish oil group. Left cerebral hemispheres among all pups were atrophic. Right cerebral hemispheres of pups in the corn oil group showed more histological evidence of edema, and had significantly higher volumes than pups in the fish oil group (66 vs. 42 mm2, p=0.007). These data suggest that the fatty acid composition of prenatal and/or postnatal diet can affect the neonatal response to excitotoxic neural injury.

DIETARY FATTY ACID (FA) EFFECTS UPON THYMOCYTE SUBSET DISTRIBUTION. † 1817

Alterations in dietary FAs are reported to affect immunity via effects upon cytokine gene expression, eicosanoid synthesis and membrane physicochemical properties. The effects of maternal diet FA composition upon thymocyte subset distribution were studied in neonatal rat pups. Methods: Timed pregnant dams were fed, beginning on day 2 of gestation and throughout lactation, either chow (control) or a purified diet whose fat source (22% of cals) was corn oil (high n6) or menhaden fish oil (high n3). On day 3 of life, pups were culled to 10 per dam and were randomly cross-fostered among dams fed the same diets to minimize litter effects. Culled pup thymuses were removed for FA analysis. On day 7 of life, pups were sacrificed and thymuses removed for flow cytometric analysis of thymocyte subsets; milk samples were collected for FA analysis. Results: Length of gestation and pup weights did not differ among diet groups. The FA composition of maternal milk and pup thymuses reflected maternal diet, with a significant enrichment of n6 and n3 FAs in the corn and fish groups, respectively (FA data shown for pup thymus only). The percent of double positive immature thymocytes (CD4+CD8+) was significantly lower in the fish versus corn group, while the percent of CD4+CD8-, CD3brtCD4brt and CD3brtCD8brt thymocytes was significantly higher in the fish versus corn and chow groups.Conclusion: The FA composition of pre- and/or postnatal diet affects the FA composition of neonatal thymus, and may influence thymocyte differentiation. (Funded in part by Ross Products Division)Table

The Effect of Dietary Docosahexanoic Acid (DHA) on Cochlear Function in Developing Rat Pups

The Effect of Dietary Docosahexanoic Acid (DHA) on Cochlear Function in Developing Rat Pups

DIETARY FATTY ACID (FA) EFFECTS UPON GROUP B STREPTOCOCCAL (GBS) INFECTION. † 1893

Dietary FA effects upon the immune response may be mediated in part by effects upon proinflammatory cytokines and eicosanoids. The impact of maternal diet FA composition upon mortality from GAS infection was studied in neonatal rat pups. Methods: Timed pregnant dams were fed, beginning on day 2 of gest. and throughout lactation, either chow (control) or a purified diet whose fat source (22% of cals) was either corn oil (high n6) or menhaden fish oil (high n3). On day 3 of life, pups were culled to 10 pups per dam and were randomly cross-fostered among dams fed the same diets to minimize litter effects. Milk was removed from culled pup stomachs for FA analysis. Exp 1: On day 7 of life, pups were injected i.p. with 0.1 ml of a suspension of GAS Type I as follows: one litter per diet with 106.5 organisms, and one litter per diet with 107.5 organisms. Data from both doses were combined for statistical analyses. Exp 2: On day 7 of life, pups (n=1 litter per diet group) were injected with 107 GAS organisms and sacrificed 48 hours later. Blood was collected for GAS culture and analysis of serum TNFα levels; spleen weights were determined. Results: FA composition of milk reflected maternal diet (Table). Exp 1: 100% of pups in the chow and corn oil groups died within 96 hours, while 33% survived in the fish oil group (p=0.002 fishers exact (permutation) test). Exp 2: Spleen weights (as% body weight) were significantly higher in the fish vs corn and chow groups. Preliminary cytokine data suggest lower serum levels of TNFα and a trend towards fewer positive blood culture in pups of the fish group. Conclusion: The FA composition pre- and/or postnatal diet may affect immune response to bacterial sepsis. Funded in part by Ross Laboratories.