Biology subjects

Pull, K.

Publications and source records attributed to Pull, K..

3 recordsLinked to original sources

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↗

bioRxiv2022

Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring

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.

neuroscience↗

bioRxiv2022

Maternal dietary choline deficiencies during pregnancy and lactation reduce cerebral blood flow in 3-month-old female mice offspring following ischemic stroke to the sensorimotor cortex

Background and PurposeAdequate maternal dietary levels of one-carbon (1C) metabolites, such as folic acid and choline, play an important role in the closure of the neural tube in utero; however, the impact of deficiencies in 1C on offspring neurological function after birth remain undefined. Stroke is one of the leading causes of death and disability globally. The aim of our study was to determine the impact of maternal 1C nutritional deficiencies on cerebral and peripheral blood flow after ischemic stroke in adult female offspring. MethodIn this study, female mice were placed on either control (CD), folic acid (FADD), or choline (ChDD) deficient diets prior to pregnancy. Female offspring were weaned onto a CD for the duration of the study. Ischemic stroke was induced in offspring and after six weeks cerebral and peripheral blood flow velocity was measured using ultrasound imaging. ResultsOur data showed that 11.5-month-old female offspring from ChDD mothers had reduced blood flow in the posterior cerebral artery compared to controls. In peripheral blood flow velocity measurements, we report an aging effect. ConclusionsThese results emphasize the importance of maternal 1C diet in early life neuro-programming on long-term vasculature health.

neuroscience↗