Ille, S. | bioRxiv Science

bioRxiv2024

Maternal dietary deficiency in choline reduced levels of MMP-2 levels in blood and brain tissue of male offspring mice

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. Its well known that maternal diet during pregnancy and lactation is vital for the early neurodevelopment of offspring. One-carbon (1C) metabolism, including folic acid and choline, plays a vital role in closure of the neural tube in utero. However, the impact of maternal dietary deficiencies in 1C on offspring neurological function following ischemic stroke later in life remains undefined. The aim of this study was to investigate inflammation in blood and brain tissue of offspring from mothers deficient in dietary folic acid or choline. Female mice were maintained on either a control or deficient diets prior to and during pregnancy and lactation. When offspring were 3-months of age, ischemic stroke was induced. One and half months later blood and brain tissue were collected. We measured levels of matrix-metalloproteases (MMP)-2 and 9 in both plasma and brain tissue, and report reduced levels of MMP-2 in both, with no changes observed in MMP-9. This observation supports our working hypothesis that maternal dietary deficiencies in folic acid or choline during early neurodevelopment impact the levels of inflammation in offspring after ischemic stroke.

neuroscience↗

bioRxiv2023

Maternal dietary deficiencies in one-carbon metabolism during early neurodevelopment result in larger damage volume, re-duced neurodegeneration and neuroinflammation and changes in choline metabolites after ischemic stroke in middle-aged offspring

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.

neuroscience↗