Perinatal choline status, metabolism, and brain development in the piglet

Choline;prenatal;postnatal;piglet;brain;metabolomics;Magnetic resonance imaging (MRI)

Getty, Caitlyn M

关键词: Choline;    prenatal;    postnatal;    piglet;    brain;    metabolomics;    Magnetic resonance imaging (MRI);   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/89137/GETTY-DISSERTATION-2015.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Although recognized as an essential nutrient in 1998, more than 90% of adults (including pregnant women) in the United States are consuming choline at levels below recommendations. Choline is required for normal neurodevelopment; but, there is relatively little research evaluating the impact of maternal choline intake on infant or childhood health, development, or intelligence outcomes. Numerous rodent studies have reported diminished performance in learning and memory tasks of offspring following choline deficiency during gestation; however, rodents may not be the most appropriate model to study early life choline status. As such, pigs were chosen as a translational model for the human infant due to striking similarities in digestive physiology, neuroanatomy, and neurodevelopmental trajectory. We hypothesized that pigs would exhibit several negative effects of choline deficiency such as: metabolic and clinical health outcomes similar to humans, learning and memory outcomes similar to rodents, and long-term neurodevelopmental and growth delays. In order to evaluate these hypotheses, two similar experiments were conducted. For both experiments, sows were provided either a choline deficient (CD) or choline sufficient (CS) diet for the last 65 d of gestation (prenatal intervention). Piglets were weaned from the sow 48 h after farrowing and provided either a CD or CS milk replacer (postnatal intervention) for 29 ± 2 d, resulting in a factorial arrangement of 4 treatment (prenatal/postnatal) groups: CS/CS, CS/CD, CD/CS, and CD/CD. To evaluate long-term impacts of choline deficiency, half of the littermate piglets in the second experiment were transferred to standard University of Illinois swine production diets at 29 ± 1 d until 89 ± 2 d of age. The first experiment evaluated the metabolomic and clinical health outcomes of perinatal choline deficiency in neonatal piglets. Overall, the piglet appears to be a sensitive model for choline deficiency during the perinatal period, as piglets did exhibit clinical health outcomes similar to humans. Specifically, liver enzymes such as ALP and GGT were elevated in postnatally CD piglets as compared to their postnatally CS counterparts. Additionally, plasma cholesterol concentrations were lower in postnatally CD piglets as compared to postnatally CS piglets, suggesting impaired VLDL excretion from the liver. In the second experiment, neurodevelopment and function were evaluated using magnetic resonance imaging procedures (macrostructural analysis, voxel-based morphometry, diffusion tensor imaging, and magnetic resonance spectroscopy) and cognitive performance in a spatial T-maze learning and memory task. We observed that perinatal choline deficiency delays brain development in terms of both overall brain size and white matter maturation, and alters hippocampal metabolite concentrations, but learning and memory performance was only minimally impacted. Additionally, long-term growth performance and health outcomes were evaluated. Provision of CS diets following the neonatal period reversed many of the observed negative impacts of perinatal choline in piglets; however, differences in growth performance persisted in older pigs. Taken together, maternal and early postnatal choline intake have both short- and long-term impacts on overall health status and growth performance of domestic pigs.