Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring

Jadavji, NafisaM; Clementson, McCoy; Hurley, Lauren; Coonrod, Sarah; Bennett, Calli; Marella, Purvaja; Pascual, AgnesS; Pull, Kasey; Wasek, Brandi; Malysheva, Olga; Caudill, MarieA

doi:10.4103/1673-5374.371375

Cited by 8 publications

(12 citation statements)

References 37 publications

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“…One-carbon (1C) metabolism is a critical biosynthetic process that is involved in the closure of the neural tube, neuronal plasticity, and cellular proliferation in the developing embryo. We have previously demonstrated that maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in offspring [34], [35]. However, there is insufficient data to understand the mechanisms involved.…”

Section: Discussionmentioning

confidence: 99%

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

Yaldiko,

Coonrod,

Marella

et al. 2023

Preprint

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Stoke is the leading cause of death and disability globally. By addressing modifiable risk factors, particularly nutrition, the prevalence of stroke and its dire consequences can be mitigated. One-carbon (1C) metabolism is a critical biosynthetic process that is involved in neural tube closure, neuronal plasticity, and cellular proliferation in the developing embryo. Folic acid and choline are two active components of 1C metabolism, we have previously demonstrated that maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in offspring. However, there is insufficient data to understand the neuronal mechanisms involved. We exposed embryonic neurons of offspring, whom mothers were on folic acid or choline deficient diets, to hypoxia conditions for 6 hours and return to normoxic conditions for 24 hours to model an ischemic stroke and reperfusion injury. To determine whether increased levels of either folic acid or choline can rescue reduced neuronal viability, we supplemented cell media with folic acid and choline prior to and after exposure to hypoxia. Our results suggest that maternal dietary deficiencies in either folic acid or choline during pregnancy negatively impacts offspring neuronal viability after hypoxia. Furthermore, increasing levels of folic acid or choline prior to and after hypoxia have a beneficial impact on neuronal viability. The findings contribute to our understanding of the intricate interplay between maternal dietary factors, 1C metabolism, and the outcome of offspring to hypoxic events, emphasizing the potential for nutritional interventions in mitigating adverse outcomes.

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Section: Discussionmentioning

confidence: 99%

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

Yaldiko,

Coonrod,

Marella

et al. 2023

Preprint

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“…Experimental manipulations are summarized in Figure 2. Two-month-old female mice were habituated for seven days before they were placed on either control (CD), folic acid (FADD, folic acid: 0.3 mg/kg), or choline deficient diets (ChDD, choline bitrate: 300 mg/kg) (Clementson et al, 2023; Dam et al, 2017; Hurley et al, 2023; Jadavji, Deng, et al, 2015; Jadavji, Farr, et al, 2015) (Envigo, Indianapolis, IN). The control diet contains the minimum amount of folic acid (2 mg/kg) and choline bitrate (1150 mg/kg).…”

Section: Methodsmentioning

confidence: 99%

“…10mg/kg of the photosensitive Rose Bengal (Sigma, St. Louis, MA) dye was injected intraperitoneally 5 minutes prior to irradiation. A 532 nm green laser was placed 3 cm above the animal and directed to the sensorimotor cortex (mediolateral + 0.24mm) (Abato et al, 2020;Clementson et al, 2023;Hurley et al, 2023;Jadavji et al, 2017Jadavji et al, , 2019Jadavji et al, , 2019Lee et al, 2004;Mbs et al, 2023;Poole et al, 2022) for 15 min.…”

Section: Photothrombosis Model For Ischemic Strokementioning

confidence: 99%

“…can modulate cerebrovascular structure and function, leading to endothelial dysfunction, reduced smooth muscle contractility, and decreased myogenic tone, all of which significantly influence peripheral and cerebral vascular health in mouse and rat adult offspring (Campbell et al, 2005; Durrant et al, 2014; Lin et al, 2018). Our group has demonstrated that maternal dietary deficiencies in folic acid or choline impact offspring ischemic stroke outcome (Clementson et al, 2023; Hurley et al, 2023; Pull et al, 2023). However, the mechanisms are not yet clear, our hypothesis is that maternal diet deficient in either folic acid or choline combined with ischemic stroke will result in changes to metabolites within the gut.…”

Section: Introductionmentioning

confidence: 99%

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Maternal dietary deficiencies in folic acid and choline change metabolites levels in offspring after ischemic stroke

Anwar,

Mosley,

Jasbi

et al. 2024

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Ischemic stroke is a debilitating disease, with nutrition being a modifiable risk factor. Changes in levels of metabolites can be used to measure the alterations in the gut, a significant marker for the etiology of diseases. This study utilized untargeted metabolomics to investigate changes in fecal samples of offspring in response to maternal dietary deficiencies and ischemic stroke. Female mice were placed on control (CD), folic acid- (FADD), or choline-deficient (ChDD) diets prior to, during pregnancy, and lactation. Offspring were weaned on to CD and at 2 months of age an ischemic stroke was induced. Fecal samples were collected prior to ischemic stroke, and at 1- and 4-weeks post-stroke for analysis. Sex and maternal dietary differences in metabolites were observed at both the 1- and 4-week post-stroke timepoints. At the 1-week post-stroke, female FADD offspring had more changes in metabolites than males. Comparatively, at the 4-week post-stroke timepoint, female offspring on either FADD or ChDD demonstrated metabolite changes. This study demonstrates a long-lasting impact of maternal dietary deficiencies on central nervous system and gut microbiome function after ischemic stroke.Summary StatementOur study investigated metabolite changes in female and male offspring fecal samples from mothers maintained on folic acid or choline deficient diet. We report that female offspring metabolite levels were impacted.

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“…Nutrition is linked to the onset of these aforementioned risk factors [7] and is a modifiable risk factor for ischemic stroke [8,9]. Previous literature has established a link between one-carbon (1C) metabolism deficiency and worse post-ischemic stroke outcome [10][11][12][13][14][15][16][17]. Folic acid and choline are the main components of 1C and are well known for their role in the closure of the neural tube of the developing fetus during pregnancy [18].…”

Section: Introductionmentioning

confidence: 99%

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

Esfandiarei,

Strash,

Covaleski

et al. 2024

Preprint

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Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It’s 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 tubein 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.

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Maternal dietary deficiencies in folic acid or choline worsen stroke outcomes in adult male and female mouse offspring

Cited by 8 publications

References 37 publications

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

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

Maternal dietary deficiencies in folic acid and choline change metabolites levels in offspring after ischemic stroke

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

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