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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

Kasey Pull, Robert Folk, Jeemin Kang, Shaley Jackson, Brikena Gusek, Mitra Esfandiarei, View ORCID ProfileNafisa M. Jadavji
doi: https://doi.org/10.1101/2022.08.23.505040
Kasey Pull
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
BA
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Robert Folk
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
BS
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Jeemin Kang
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
2College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
MA
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Shaley Jackson
3College of Veterinary Medicine, Midwestern University, Glendale, AZ, USA
BSc
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Brikena Gusek
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
BS
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Mitra Esfandiarei
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
3College of Veterinary Medicine, Midwestern University, Glendale, AZ, USA
4Basic Medical Sciences, College of Medicine Phoenix, University of Arizona, Phoenix, AZ, USA
5Anesthesiology, Pharmacology, & Therapeutics, Faculty of Medicine, University of British Columbia, BC, Canada
PhD
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Nafisa M. Jadavji
1Department of Biomedical Sciences, Midwestern University, Glendale, AZ, USA
2College of Osteopathic Medicine, Midwestern University, Glendale, AZ, USA
3College of Veterinary Medicine, Midwestern University, Glendale, AZ, USA
6Department of Neuroscience, Carleton University, Ottawa, ON, Canada
PhD
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  • ORCID record for Nafisa M. Jadavji
  • For correspondence: njadav@midwestern.edu
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Abstract

A maternal diet that provides adequate nutrition during pregnancy and lactation is vital to the neurodevelopment of offspring. One-carbon metabolism plays an important role in the closure of the neural tube of the developing embryo; however, the impact of maternal one-carbon dietary deficiencies on offspring neurological function later in life remains relatively unknown. 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. The aim of our study was to determine the impact of maternal nutritional deficiencies on cerebral blood flow and peripheral hemodynamics after ischemic stroke in adult offspring. In this study, adult female C57BL/6J mice were placed on either control (CD), choline (ChDD) or folic acid (FADD) deficient diets for four weeks to deplete stores prior to mating and maintained on the assigned diet during pregnancy and lactation. Female offspring were weaned and transitioned to a CD for the duration of the study. Ischemic stroke was induced in the sensorimotor cortex of 2- and 10-month-old female offspring using the photothrombosis model. Six weeks after induction of stroke, cerebral and peripheral blood flow was measured using the Vevo2100 Pulse Wave Doppler tracing modality. Our data showed that 3.5-month-old female offspring from a ChDD mothers had reduced blood flow in the posterior cerebral artery compared to CD mice; this effect disappeared in older offspring. In 11.5-month-old females we observed changes in peripheral hemodynamics, but not in young animals. Our findings suggest that a maternal dietary deficiency in choline results in reduced cerebral blood flow in adult female offspring after ischemic stroke, but the long-term effects are not present. This result points to the key role of the maternal diet in early life neuro-programming, while emphasizing its effects on both fetal development and long-term cerebrovascular health.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 25, 2022.
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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
Kasey Pull, Robert Folk, Jeemin Kang, Shaley Jackson, Brikena Gusek, Mitra Esfandiarei, Nafisa M. Jadavji
bioRxiv 2022.08.23.505040; doi: https://doi.org/10.1101/2022.08.23.505040
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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
Kasey Pull, Robert Folk, Jeemin Kang, Shaley Jackson, Brikena Gusek, Mitra Esfandiarei, Nafisa M. Jadavji
bioRxiv 2022.08.23.505040; doi: https://doi.org/10.1101/2022.08.23.505040

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