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Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

ABSTRACT: Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline supply between embryonic day (E)11 and E17 of gestation, the number of 2 types of cortical neural progenitor cells (NPCs)-radial glial cells and intermediate progenitor cells-was reduced in fetal brains (P< 0.01). Furthermore, the number of upper layer cortical neurons was decreased in the offspring of dams fed an LC diet at both E17 (P< 0.001) and 4 mo of age (P< 0.001). These effects of LC maternal diet were mediated by a decrease in epidermal growth factor receptor (EGFR) signaling in NPCs related to the disruption of EGFR posttranscriptional regulation. Our findings describe a novel mechanism whereby low maternal dietary intake of choline alters brain development.-Wang, Y., Surzenko, N., Friday, W. B., Zeisel, S. H. Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

SUBMITTER: Wang Y

PROVIDER: S-EPMC4799499 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

Wang Yanyan Y Surzenko Natalia N Friday Walter B WB Zeisel Steven H SH

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20151223 4

Maternal diets low in choline, an essential nutrient, increase the risk of neural tube defects and lead to low performance on cognitive tests in children. However, the consequences of maternal dietary choline deficiency for the development and structural organization of the cerebral cortex remain unknown. In this study, we fed mouse dams either control (CT) or low-choline (LC) diets and investigated the effects of choline on cortical development in the offspring. As a result of a low choline sup ...[more]

PMID: 26700730

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Project description:BACKGROUND:Consistent evidence of an influence of maternal dietary intake during pregnancy on infant body size and composition in human populations is lacking, despite robust evidence in animal models. OBJECTIVE:We sought to evaluate the influence of maternal macronutrient intake and balance during pregnancy on neonatal body size and composition, including fat mass and fat-free mass. STUDY DESIGN:The analysis was conducted among 1040 mother-offspring pairs enrolled in the prospective prebirth observational cohort: the Healthy Start Study. Diet during pregnancy was collected using repeated 24-hour dietary recalls (up to 8). Direct measures of body composition were obtained using air displacement plethysmography. The National Cancer Institute measurement error model was used to estimate usual dietary intake during pregnancy. Multivariable partition (nonisocaloric) and nutrient density (isocaloric) linear regression models were used to test the associations between maternal dietary intake and neonatal body composition. RESULTS:The median macronutrient composition during pregnancy was 32.2% from fat, 15.0% from protein, and 47.8% from carbohydrates. In the partition multivariate regression model, individual macronutrient intake values were not associated with birthweight or fat-free mass, but were associated with fat mass. Respectively, 418 kJ increases in total fat, saturated fat, unsaturated fat, and total carbohydrates were associated with 4.2-g (P = .03), 11.1-g (P = .003), 5.9-g (P = .04), and 2.9-g (P = .02) increases in neonatal fat mass, independent of prepregnancy body mass index. In the nutrient density multivariate regression model, macronutrient balance was not associated with fat mass, fat-free mass, or birthweight after adjustment for prepregnancy body mass index. CONCLUSION:Neonatal adiposity, but not birthweight, is independently associated with increased maternal intake of total fat, saturated fat, unsaturated fat, and total carbohydrates, but not protein, suggesting that most forms of increased caloric intake contribute to fetal fat accretion.

Project description:BackgroundCholine is an essential nutrient that is pivotal to proper brain development. Research in animal models suggests that perinatal choline deficiency influences neuron development in the hippocampus and cortex, yet these observations require invasive techniques.ObjectiveThis study aimed to characterize the effects of perinatal choline deficiency on gray and white matter development with the use of noninvasive neuroimaging techniques in young pigs.MethodsDuring the last 64 d of the 114-d gestation period Yorkshire sows were provided with a choline-sufficient (CS) or choline-deficient (CD) diet, analyzed to contain 1214 mg or 483 mg total choline/kg diet, respectively. Upon farrowing, pigs (Sus scrofa domesticus) were allowed colostrum consumption for ≤48 h, were further stratified into postnatal treatment groups, and were provided either CS or CD milk replacers, analyzed to contain 1591 or 518 mg total choline/kg diet, respectively, for 28 d. At 30 d of age, pigs were subjected to MRI procedures to assess brain development. Gray and white matter development was assessed through voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) to assess the effects of prenatal and postnatal dietary choline status.ResultsVBM analysis indicated that prenatally CS pigs exhibited increased (P < 0.01) gray matter in the left and right cortex compared with prenatally CD pigs. Analysis of white matter indicated that prenatally CS pigs exhibited increased (P < 0.01) white matter in the internal capsule, putamen-globus pallidus, and right cortex compared with prenatally CD pigs. No postnatal effects (P > 0.05) of choline status were noted for VBM analyses of gray and white matter. TBSS also showed no significant effects (P > 0.05) of prenatal or postnatal choline status for diffusion values along white matter tracts.ConclusionsObservations from this study suggest that prenatal choline deficiency results in altered cortical gray matter and reduced white matter in the internal capsule and putamen of young pigs. With the use of noninvasive neuroimaging techniques, results from our study indicate that prenatal choline deficiency greatly alters gray and white matter development in pigs, thereby providing a translational assessment that may be used in clinical populations.

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Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

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Maternal dietary intake of choline in mice regulates development of the cerebral cortex in the offspring.

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