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Updated: Jun 11, 2026

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Low ascorbic acid and increased oxidative stress in gulo(-/-) mice during development.

Fiona E Harrison1, M Elizabeth Meredith, Sean M Dawes

  • 1Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA. Fiona.Harrison@Vanderbilt.edu

Brain Research
|July 6, 2010
PubMed
Summary

Vitamin C deficiency in developing mice lacking ascorbic acid (AA) synthesis causes significant oxidative stress, particularly in the brain. This highlights AA's crucial role in preventing developmental damage.

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Area of Science:

  • Developmental biology
  • Neuroscience
  • Biochemistry

Background:

  • Vitamin C (ascorbic acid, AA) depletion during development can cause irreversible damage.
  • The gulonolactone oxidase (gulo) knockout mouse model is unable to synthesize AA, similar to humans.

Purpose of the Study:

  • To investigate the relationship between AA deficiency and oxidative stress during prenatal and postnatal development.
  • To assess the impact of AA deficiency on brain function and organ health in gulo knockout mice.

Main Methods:

  • Utilized gulo knockout mice (gulo-/-) and heterozygous controls (gulo+/-) for breeding.
  • Measured AA levels, malondialdehyde (MDA), and F(2)-isoprostanes at embryonic day 20 (E20), postnatal day 1 (P1), day 10 (P10), and day 18 (P18).
  • Assessed total glutathione levels as an indicator of antioxidant system activation.

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Main Results:

  • Gulo(-/-) pups showed significantly lower AA levels and increased oxidative stress markers (MDA, F(2)-isoprostanes) by P10 and P18.
  • Sufficient AA transfer during pregnancy protected E20 and P1 pups.
  • Elevated glutathione levels in gulo(-/-) mice indicated a compensatory antioxidant response.

Conclusions:

  • AA deficiency directly correlates with increased oxidative stress in developing gulo(-/-) mice.
  • Ascorbic acid is critical for preventing oxidative stress in the developing brain of species that cannot synthesize it.
  • Findings underscore the importance of adequate AA levels during critical developmental periods.