ArticlePloS one2013
Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- p-Cresol and p-Cresyl Sulphate Boost Oxidative Stress: A Systematic Review of Recent Evidence.Basic & clinical pharmacology & toxicology · 2025Pooled it
- RNA imbalance as a hallmark of cellular ageing.Nature cell biology · 2026Review
- Article
- Sex-dependent epigenetic disruption of YY1 binding by prenatal BPA exposure downregulates Matr3 and alters Agap1 splicing in the offspring hippocampus.Biology of sex differences · 2025Article
- Article
- Posttranslational Regulation of Mammalian Sulfur Amino Acid Metabolism.International journal of molecular sciences · 2025Review
- Article
- Genetic etiology of autism spectrum disorder in the African population: a scoping review.Frontiers in genetics · 2024Article
- Article
- Psychostimulants influence oxidative stress and redox signatures: the role of DNA methylation.Redox report : communications in free radical research · 2022Review
- Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies.Nutrients · 2022Review
- Maternal prenatal selenium levels and child risk of neurodevelopmental disorders: A prospective birth cohort study.Autism research : official journal of the International Society for Autism Research · 2021Article
- The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.Journal of personalized medicine · 2021Review
- Potential Novel Therapies for Neurodevelopmental Diseases Targeting Oxidative Stress.Oxidative medicine and cellular longevity · 2021Review
- DNA Methylation Associated with Mitochondrial Dysfunction in a South African Autism Spectrum Disorder Cohort.Autism research : official journal of the International Society for Autism Research · 2020Article
- Oxidative, Reductive, and Nitrosative Stress Effects on Epigenetics and on Posttranslational Modification of Enzymes in Cardiometabolic Diseases.Oxidative medicine and cellular longevity · 2020Review
- Comparison of Three Clinical Trial Treatments for Autism Spectrum Disorder Through Multivariate Analysis of Changes in Metabolic Profiles and Adaptive Behavior.Frontiers in cellular neuroscience · 2018Article
- Comparison of Treatment for Metabolic Disorders Associated with Autism:Reanalysis of Three Clinical Trials.Frontiers in neuroscience · 2018Article
- Mathematical modeling of the methionine cycle and transsulfuration pathway in individuals with autism spectrum disorder.Journal of theoretical biology · 2017Article
- Short-term sleep deprivation leads to decreased systemic redox metabolites and altered epigenetic status.PloS one · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The folate and vitamin B12-dependent enzyme methionine synthase (MS) is highly sensitive to cellular oxidative status, and lower MS activity increases production of the antioxidant glutathione, while simultaneously decreasing more than 200 methylation reactions, broadly affecting metabolic activity. MS mRNA levels in postmortem human cortex from subjects across the lifespan were measured and a dramatic progressive biphasic decrease of more than 400-fold from 28 weeks of gestation to 84 years was observed. Further analysis revealed alternative splicing of MS mRNA, including deletion of folate-binding domain exons and age-dependent deletion of exons from the cap domain, which protects vitamin B12 (cobalamin) from oxidation. Although three species of MS were evident at the protein level, corresponding to full-length and alternatively spliced mRNA transcripts, decreasing mRNA levels across the lifespan were not associated with significant changes in MS protein or methionine levels. MS mRNA levels were significantly lower in autistic subjects, especially at younger ages, and this decrease was replicated in cultured human neuronal cells by treatment with TNF-α, whose CSF levels are elevated in autism. These novel findings suggest that rather than serving as a housekeeping enzyme, MS has a broad and dynamic role in coordinating metabolism in the brain during development and aging. Factors adversely affecting MS activity, such as oxidative stress, can be a source of risk for neurological disorders across the lifespan via their impact on methylation reactions, including epigenetic regulation of gene expression.
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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.