ArticleGenes, brain, and behavior2012
Effect of vitamin C deficiency during postnatal development on adult behavior: functional phenotype of Gulo-/- knockout mice.
Article in Genes, brain, and behavior, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- The neuropsychiatric effects of vitamin C deficiency: a systematic review.BMC psychiatry · 2020Pooled it
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- Threshold Effects of Maternal Vitamin C in Late Pregnancy on Infant Social Competence: A Nonlinear Dose-Response Analysis in a Birth Cohort.Food science & nutrition · 2026Article
- Ameliorative Effect of Vitamin C Against Tramadol-Induced Learning and Memory Impairment in Juvenile Rat Via Attenuation of Oxidative Stress and Dysfunctional Synaptic Plasticity.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Gene-dose effect of the glutathione biosynthesis gene on ascorbate deficiency in mice.Biochemical and biophysical research communications · 2025Article
- Role of channels in the ObioRxiv : the preprint server for biology · 2025Article
- Disturbances of the Lung Glutathione System in Adult Guinea Pigs Following Neonatal Vitamin C or Cysteine Deficiency.Antioxidants (Basel, Switzerland) · 2023Article
- Reply to Charles V. Vorhees: Aspartame and anxiety-like behavior.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Fatal Epileptic Seizures in Mice Having Compromised Glutathione and Ascorbic Acid Biosynthesis.Antioxidants (Basel, Switzerland) · 2023Article
- Ascorbate Is a Primary Antioxidant in Mammals.Molecules (Basel, Switzerland) · 2022Review
- Opioids and Vitamin C: Known Interactions and Potential for Redox-Signaling Crosstalk.Antioxidants (Basel, Switzerland) · 2022Review
- Vitamin C deficiency reveals developmental differences between neonatal and adult hematopoiesis.Frontiers in immunology · 2022Article
- Role of vitamin C in preventing of COVID-19 infection, progression and severity.AIMS microbiology · 2022Review
- Pleiotropic Actions of Aldehyde Reductase (AKR1A).Metabolites · 2021Review
- Review
- Decreased content of ascorbic acid (vitamin C) in the brain of knockout mouse models of Na+,K+-ATPase-related neurologic disorders.PloS one · 2021Article
- (Ascorb)ing Pb Neurotoxicity in the Developing Brain.Antioxidants (Basel, Switzerland) · 2020Review
- Ascorbic acid insufficiency impairs spatial memory formation in juvenile AKR1A-knockout mice.Journal of clinical biochemistry and nutrition · 2019Article
- Vitamin C as a Modulator of the Response to Cancer Therapy.Molecules (Basel, Switzerland) · 2019Review
- Preventive and Therapeutic Potential of Vitamin C in Mental Disorders.Current medical science · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Organisms using oxygen for aerobic respiration require antioxidants to balance the production of reactive oxygen species during metabolic processes. Various species--including humans and other primates--suffer mutations in the GULO gene encoding L-gulono-γ-lactone oxidase; GULO is the rate-limiting enzyme in the biosynthesis of ascorbate, an important cellular antioxidant. Animals lacking the ability to synthesize vitamin C develop scurvy without dietary supplementation. The Gulo-/- knockout (KO) mouse requires oral supplemental vitamin C; without this supplementation the animal dies with a scorbutic condition within several weeks. Vitamin C is known to be most abundant in the brain, where it is believed to play important roles in neuroprotection, neurotransmission and neuromodulation. We therefore hypothesized that ascorbate deficiency in Gulo-/- KO mice might lead to an abnormal behavioral phenotype. We established the amount of ascorbate in the drinking water (220 ppm) necessary for generating a chronic low-ascorbate status in the brain, yet clinically the mice appeared healthy throughout 100 days postpartum at which time all behavioral-phenotyping tests were completed. Compared with Gulo+/+ wild-type littermates, ascorbate-deficient Gulo-/- mice were found to be less active in moving in their environment; when in water, these mice swam more slowly in some tests, consistent with a mild motor deficit. We found no evidence of cognitive, anxiety or sensorimotor-gating problems. Despite being less active, Gulo-/- mice exhibited exaggerated hyperactivity to the dopaminergic agonist methamphetamine. The subnormal movement, combined with hypersensitivity to a dopamine agonist, point to developmental ascorbate deficiency causing long-term striatal dysfunction.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.