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5. Maternal vitamin C deficiency during pregnancy persistently impairs hippocampal neurogenesis in offspring of guinea pigs

Author

Tveden-Nyborg, Pernille, Vogt, Lucile, Schjoldager, Janne Gram, Jeannet, Natalie, Andersen, Stine Hasselholt, Paidi, Maya Devi, Christen, Stephan, Lykkesfeldt, Jens, Tveden-Nyborg, Pernille, Vogt, Lucile, Schjoldager, Janne Gram, Jeannet, Natalie, Andersen, Stine Hasselholt, Paidi, Maya Devi, Christen, Stephan, and Lykkesfeldt, Jens

Abstract

While having the highest vitamin C (VitC) concentrations in the body, specific functions of VitC in the brain have only recently been acknowledged. We have shown that postnatal VitC deficiency in guinea pigs causes impairment of hippocampal memory function and leads to 30% less neurons. This study investigates how prenatal VitC deficiency affects postnatal hippocampal development and if any such effect can be reversed by postnatal VitC repletion. Eighty pregnant Dunkin Hartley guinea pig dams were randomized into weight stratified groups receiving High (900 mg) or Low (100 mg) VitC per kg diet. Newborn pups (n = 157) were randomized into a total of four postnatal feeding regimens: High/High (Control); High/Low (Depleted), Low/Low (Deficient); and Low/High (Repleted). Proliferation and migration of newborn cells in the dentate gyrus was assessed by BrdU labeling and hippocampal volumes were determined by stereology. Prenatal VitC deficiency resulted in a significant reduction in postnatal hippocampal volume (P

Published
2012

7. Reproducibility of preclinical animal research improves with heterogeneity of study samples

Author

Voelkl, Bernhard, Vogt, Lucile, Sena, Emily S, and Würbel, Hanno

Subjects
630 Agriculture, 3. Good health
Abstract

Single-laboratory studies conducted under highly standardized conditions are the gold standard in preclinical animal research. Using simulations based on 440 preclinical studies across 13 different interventions in animal models of stroke, myocardial infarction, and breast cancer, we compared the accuracy of effect size estimates between single-laboratory and multi-laboratory study designs. Single-laboratory studies generally failed to predict effect size accurately, and larger sample sizes rendered effect size estimates even less accurate. By contrast, multi-laboratory designs including as few as 2 to 4 laboratories increased coverage probability by up to 42 percentage points without a need for larger sample sizes. These findings demonstrate that within-study standardization is a major cause of poor reproducibility. More representative study samples are required to improve the external validity and reproducibility of preclinical animal research and to prevent wasting animals and resources for inconclusive research.

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