Maternal one-carbon (1C) metabolism plays an important role in early life programming. There is a well-established connection between the fetal environment and the health status of the offspring. However, there is a knowledge gap on how maternal nutrition impacts stroke outcome in offspring. The aim of our study was to investigate the role of maternal dietary deficiencies in folic acid or choline on stroke outcome in 3-month-old offspring. Adult female mice were fed a folic acid deficient diet (FADD), choline deficient diet (ChDD), or control diet (CD) prior to pregnancy. They were continued on diets during pregnancy and lactation. Male and female offspring were weaned onto a CD and at 2 months of age were subject to ischemic stroke within the sensorimotor cortex via photothrombosis damage. At 3-months-of-age, motor function was measured in offspring and tissue was collected for analysis. Mothers maintained on either a FADD or ChDD had reduced levels of S-adenosylmethionine in liver and S-adenosylhomocysteine in plasma. After ischemic stroke, motor function was impaired in 3-month-old offspring from deficient mothers compared to CD animals. In brain tissue, there was no difference in ischemic damage volume. When protein levels were assessed in brain tissue, there were lower levels of neurodegeneration in males compared to females and betaine levels were reduced in offspring from ChDD mothers. Our results demonstrate that a deficient maternal diet during critical timepoints in neurodevelopment results in worse stroke outcomes. This study emphasizes the importance of maternal diet and the impact it can have on offspring health.
Maternal dietary levels of one-carbon (1C) metabolites (folic acid and choline) during pregnancy play a vital role in neurodevelopment. However, the impact of maternal dietary deficiencies on offspring stroke outcomes later in life remains undefined. The aim of this study was to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcomes in middle-aged offspring. Female mice were maintained on either a control or deficient diet prior to and during pregnancy and lactation. At 10 months of age ischemic stroke was induced in male and female offspring. Stroke outcome was assessed by measuring motor function and brain tissue. There was no difference in offspring motor function; however, sex differences were present. In brain tissue, maternal dietary deficiency increased ischemic damage volume and offspring from deficient mothers had reduced neurodegeneration and neuroinflammation within the ischemic region. Furthermore, there were changes in plasma 1C metabolites as a result of maternal diet and sex. Our data indicate that maternal dietary deficiencies do not impact offspring behavior after ischemic stroke but do play a role in brain histology and one-carbon metabolite levels in plasma. Additionally, this study demonstrates that the sex of mice plays an important role in stroke outcomes.
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 diet pregnancy and lactation is vital to the early life neuro programming of offspring. One-carbon (1C) metabolism, which includes folic acid and choline, plays a vital role in closure of the neural tube and other neurodevelopment. However, the impact of maternal dietary deficiencies on offspring neurological function following ischemic stroke later in life remains undefined. 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, our group has shown that dietary deficiencies in 1C metabolism result in worse stroke outcome. Our study aimed to investigate the role of maternal dietary deficiencies in folic acid and choline on ischemic stroke outcome in middle-aged male and female mice. Female mice were maintained on either a control or deficient diets prior to and during pregnancy and lactation. When female and male offspring were 10-months of age, ischemic stroke was induced via photothrombosis targeting the sensorimotor cortex. Stroke outcome was assessed by measuring motor function in living animals and ischemic damage volume, neurodegeneration, neuroinflammation, and choline metabolism in the brain postmortem. No significant difference was observed between maternal dietary groups in offspring motor function; however, males and females differed in their motor function. Maternal diet significantly impacted ischemic damage volume. Male and female offspring from deficient mothers showed significantly reduced neurodegeneration and neuroinflammation within the ischemic damage region. We also report changes in plasma 1C metabolites as a result of maternal diet and sex after ischemic stroke in offspring. Our data indicates that maternal dietary deficiencies do not impact offspring motor outcome following ischemic stroke, but do play a role in other ischemic stroke outcomes such as ischemic damage volume and plasma 1C metabolites in middle-aged adult offspring. Furthermore, our data indicates that sex of mice plays an important role in stroke outcome during middle-age.
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