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

Clementson, M.; Hurley, L.; Coonrod, S.; Bennett, C.; Marella, P.; Pascual, A.; Pull, K.; Bottiglieri, T.; Patterson, B.; Malysheva, O.; Caudill, M.; Jadavji, N. M.

doi:10.1101/2022.09.28.509960

bioRxiv · 10.1101/2022.09.28.509960

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

Clementson, M.·Hurley, L.·Coonrod, S.·Bennett, C.·Marella, P.·Pascual, A.·Pull, K.·Bottiglieri, T.·Patterson, B.·Malysheva, O.·Caudill, M.·Jadavji, N. M.

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Abstract

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.

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Clementson, M., Hurley, L., Coonrod, S., Bennett, C., Marella, P., Pascual, A., Pull, K., Bottiglieri, T., Patterson, B., Malysheva, O., Caudill, M., Jadavji, N. M.. 2022-10-03. Maternal dietary deficiencies in folates or choline during pregnancy and lactation worsen stroke outcome in 3-month-old male and female mouse offspring. https://doi.org/10.1101/2022.09.28.509960

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