ArticleRedox biology2022
SVCT2-mediated ascorbic acid uptake buffers stress responses via DNA hydroxymethylation reprogramming of S100 calcium-binding protein A4 gene.
Article in Redox biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- Pooled it
- Epigenetic Modulation by Vitamin C and in Prenatal Depression: Implications for Offspring Health.Current medical science · 2026Review
- Article
- Ascorbic acid enhances antidepressant-like efficacy of esketamine: Hippocampal TARP-γ8-containing AMPA receptors mediate synaptic modulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Dissolvable microneedle-assisted transdermal administration of diacerein nanoparticles achieved satisfactory therapeutic effects in tendon-bone insertion repair by reducing oxidative stress and inflammation.Materials today. Bio · 2025Article
- Costunolide normalizes neuroinflammation and improves neurogenesis deficits in a mouse model of depression through inhibiting microglial Akt/mTOR/NF-κB pathway.Acta pharmacologica Sinica · 2025Article
- Pharmacological mechanism of natural antidepressants: the role of epigenetic modifications.Frontiers in pharmacology · 2025Review
- Depression score and body mass index mediate the association between dietary vitamin C intake and female infertility: a study based on NHANES 2013-2018.Frontiers in nutrition · 2025Article
- Ascorbic acid alleviates rheumatoid arthritis by inhibiting the production of autoantibodies.Cell communication and signaling : CCS · 2024Article
- Proteomic insights into mental health status: plasma markers in young adults.Translational psychiatry · 2024Article
- Antioxidants in neuropsychiatric disorder prevention: neuroprotection, synaptic regulation, microglia modulation, and neurotrophic effects.Frontiers in neuroscience · 2024Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vitamin C, a key antioxidant in the central nervous system, cycles between ascorbic acid and dehydroascorbic acid under pathophysiological conditions. Clinical evidence supports that the absence of vitamin C may be linked to depressive symptoms, but much less is known about the mechanism. Herein, we show that chronic stress disrupts the expression of ascorbic acid transporter, sodium-dependent vitamin C transport 2, and induces a deficiency in endogenous ascorbic acid in the medial prefrontal cortex, leading to depressive-like behaviors by disturbing redox-dependent DNA methylation reprogramming. Attractively, ascorbic acid (100 mg/kg-1000 mg/kg, intraperitoneal injection, as bioequivalent of an intravenous drip dose of 0.48 g-4.8 g ascorbic acid per day in humans) produces rapid-acting antidepressant effects via triggering DNA demethylation catalyzed by ten-eleven translocation dioxygenases. In particular, the mechanistic studies by both transcriptome sequencing and methylation sequencing have shown that S100 calcium binding protein A4, a potentially protective factor against oxidative stress and brain injury, mediates the antidepressant activity of ascorbic acid via activating erb-b2 receptor tyrosine kinase 4 (ErbB4)-brain derived neurotrophic factor (BDNF) signaling pathway. Overall, our findings reveal a novel nutritional mechanism that couples stress to aberrant DNA methylation underlying depressive-like behaviors. Therefore, application of vitamin C may be a potential strategy for the treatment of depression.
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Registered trials
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