Maternal Dietary Choline Deficiencies Reduce Cerebral Blood Flow in Three-Month-Old Female Mouse Offspring Following Ischemic Stroke to the Sensorimotor Cortex

Abstract

Objectives A maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. Deficiencies in nutrients during fetal growth can lead to altered early life nutritional programming such as spina bifida, a neural tube defect. One-carbon metabolism plays a vital role in the closure of the neural tube of the developing embryo; however, the impact of maternal dietary deficiencies on offspring neurological function later in life remains relatively unknown. Stroke is one of the leading causes of death globally, and its prevalence is expected to increase in younger age groups as the incidence of various risk factors for stroke increases. Furthermore, dietary deficiencies in one-carbon metabolism are a major risk factor for ischemic stroke. The aim of our study was to determine the impact of maternal nutritional deficiencies on cerebral and peripheral blood flow after ischemic stroke in adult offspring. Methods Adult female C57BL/6J mice were placed on either control (CD), choline (ChDD) or folic acid (FD) deficient diets for four weeks to deplete stores prior to mating. Females were maintained on the assigned diet during pregnancy and lactation. Offspring were weaned onto a control diet. Ischemic stroke was induced in the sensorimotor cortex of 2-month-old female (n = 18) offspring using the photothrombosis model. Four weeks after induction of stroke, peak velocity measurements were taken using Pulse Wave Doppler tracing of the posterior cerebral artery. The data was analyzed by 2 individuals blinded to experimental groups and statistical analysis involved conducting a one-way ANOVA followed by Tukey's pairwise comparison for any significant main effects. Results Female offspring from ChDD mothers had reduced blood flow in the posterior cerebral artery compared to CD mice. We did not observe any changes in offspring from FD dams. Conclusions The findings of our study suggest that a maternal diet deficient in choline results in reduced blood flow in female offspring after ischemic stroke. This result points to the important role of the maternal diet in early life programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health. Additional studies are currently underway to measure blood flow in males and analyze peripheral blood flow in all offspring. Funding Sources AHA and NIH.

Maternal dietary deficiencies in folic acid or choline reduce primary neuron viability after exposure to hypoxia through increased levels of apoptosis

“…An example of nutritional link to ischemic stroke is one-carbon (1C) metabolism which integrates nutritional signals with several biosynthetic processes, redox homeostasis, and epigenetics [10]- [12]. The nutrient, choline and B-vitamin, folic acid, are central to 1C.…”