Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice – PubMed Black Hawk Supplements

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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 is 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…
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Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice - PubMed

Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice

Mitra Esfandiarei et al. Cells. .

Abstract

Ischemic stroke is one of the leading causes of disability and death globally, with a rising incidence in younger age groups. It is 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 the 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 diet prior to and during pregnancy and lactation. When offspring were 3 months of age, ischemic stroke was induced. One and a 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 reported reduced levels of MMP-2 in ChDD male offspring in both tissue types. No changes were 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.

Keywords: choline; folic acid; ischemic stroke; maternal nutrition; offspring; one-carbon metabolism.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1

Experimental timeline of study. At 2 months of age, female mice were placed on a control (CD), folic acid (FADD), or choline-deficient (ChDD) diet. Females were maintained on diets for the duration of pregnancy and lactation until the offspring were weaned. Once female and male offspring were weaned, they were maintained on the CD. At 2 months of age, the offspring were subjected to ischemic stroke via a unilateral photothrombosis model. At 3.5 months, female and male offspring were euthanized, and blood and brain tissues were collected for analysis.

Figure 2
Figure 2

Impact of maternal diets deficient in folic acid (FADD) or choline (ChDD) and control diet (CD) during pregnancy and lactation on levels of matrix metalloproteases (MMPs)-2 (A) and 9 (B) in plasma of female and male offspring 1 month after ischemic stroke. Mean ± SEM of 10 to 14 animals per group. * p < 0.05, Tukey’s pairwise post hoc analysis between male FADD and ChDD offspring.

Figure 3
Figure 3

Impact of maternal diets deficient in folic acid (FADD) or choline (ChDD) and the control diet (CD) during pregnancy and lactation on neuronal levels of matrix metalloprotease (MMP)-2 in ischemic brain tissue of female and male offspring one month after ischemic stroke. Representative images of MMP-2 immunofluorescence colocalization with neuronal nuclei (NeuN) and 4′,6-diamidino-2-phenylindole (DAPI) (A) and semi-quantitative quantification of MMP-2 levels within ischemic region of brain tissue (B). Mean ± SEM of 3 to 4 animals per group. * p < 0.05, Tukey’s pairwise post hoc analysis between male CD and ChDD offspring (one-way ANOVA analysis between males and significant maternal diet main effect). Magnification 200X, scale bar 50 µm.

Figure 4
Figure 4

Impact of maternal diets deficient in folic acid (FADD) or choline (ChDD) and the control diet (CD) during pregnancy and lactation on neuronal levels of MMP-9 in the ischemic brain tissue of female and male offspring one month after ischemic stroke. Representative images of matrix metalloprotease (MMP)-9 immunofluorescence colocalization with neuronal nuclei (NeuN) and 4′,6-diamidino-2-phenylindole (DAPI) (A) and semi-quantitative quantification of MMP-9 levels within ischemic region of brain tissue (B). Mean ± SEM of 3 to 4 animals per group. Magnification 200×, scale bar 50 µm.

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Maternal Dietary Deficiency in Choline Reduced Levels of MMP-2 Levels in Blood and Brain Tissue of Male Offspring Mice – PubMed