ArticleMolecular psychiatry2017
Nrf2-dependent persistent oxidative stress results in stress-induced vulnerability to depression.
Article in Molecular psychiatry, 2017. 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 108 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 239 citations in OpenAlex.
- Research trends and hotspots of electroacupuncture for depression: a bibliometric and visual analysis (2005-2025).Frontiers in psychiatry · 2026Pooled it
- Are Resistance Training-Induced BDNF in Hemodialysis Patients Associated with Depressive Symptoms, Quality of Life, Antioxidant Capacity, and Muscle Strength? An Insight for the Muscle-Brain-Renal Axis.International journal of environmental research and public health · 2021Trial
- Sex-specific regulation of angiogenin in Alzheimer's disease.Molecular psychiatry · 2026Article
- Integrated biomarkers of oxidative stress NLRP3 inflammasome and kynurenine pathway reflect disease severity and diagnostic discrimination in depression.Scientific reports · 2026Article
- Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts.Antioxidants (Basel, Switzerland) · 2026Article
- Chitosan Nanoparticles Co-Encapsulating Selegiline Analogue and L-Tyrosine Mitigate Depression-Related Pathology and Cognitive Decline in Rats.Biomolecules · 2026Article
- Oxidative Stress in Treatment-Resistant and Refractory Depression: A Hidden Therapeutic Target?Molecular neurobiology · 2026Review
- Astrocytic PERK Deficiency Drives Prefrontal Circuit Dysfunction and Depressive-Like Behaviors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Psychological Subtypes and Intervention Strategies in Burning Mouth Syndrome: A Narrative Review.Journal of pain research · 2026Review
- Mangiferin Mitigates Ketamine-Induced Dopaminergic and Glial Dysregulation and Modulates Nrf2 Expression in a Rat Schizophrenia-Like Model.Journal of experimental pharmacology · 2026Article
- An Overview of the Antioxidant, Anti-inflammatory, and Anticancer Effects of Statins.Anti-cancer agents in medicinal chemistry · 2026Review
- The Role of Stress in Burning Mouth Syndrome Triggered by Dental Treatments: A Two-Step Hypothesis.Journal of oral rehabilitation · 2025Article
- Yi-Nao-Jie-Yu Prescription Relieves Post-Stroke Depression by Mitigating Ferroptosis in Hippocampal Neurons Via Activating the Nrf2/GPX4/SLC7A11 Pathway.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- TCE-mediated neuroprotection against rotenone-induced dopaminergic neuronal death in PD mice: insights into the Nrf-2/PINK1/Parkin-mitophagy pathway.Metabolic brain disease · 2025Article
- Agomelatine Alleviates Depressive-like Behaviors by Suppressing Hippocampal Oxidative Stress in the Chronic Social Defeat Stress Model.Antioxidants (Basel, Switzerland) · 2025Article
- Discovery of Herbal Remedies and Key Components for Major Depressive Disorder Through Biased Random Walk Analysis on a Multiscale Network.International journal of molecular sciences · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Mitochondria and the Repurposing of Diabetes Drugs for Off-Label Health Benefits.International journal of molecular sciences · 2025Review
- Social isolation: an integrated molecular web that disrupts cellular homeostasis.Frontiers in neuroscience · 2025Review
- Ferroptosis-associated signaling pathways and therapeutic approaches in depression.Frontiers in neuroscience · 2025Review
48 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stressful life events produce a state of vulnerability to depression in some individuals. The mechanisms that contribute to vulnerability to depression remain poorly understood. A rat model of intense stress (social defeat (SD), first hit) produced vulnerability to depression in 40% of animals. Only vulnerable animals developed a depression-like phenotype after a second stressful hit (chronic mild stress). We found that this vulnerability to depression resulted from a persistent state of oxidative stress, which was reversed by treatment with antioxidants. This persistent state of oxidative stress was due to low brain-derived neurotrophic factor (BDNF) levels, which characterized the vulnerable animals. We found that BDNF constitutively controlled the nuclear translocation of the master redox-sensitive transcription factor Nrf2, which activates antioxidant defenses. Low BDNF levels in vulnerable animals prevented Nrf2 translocation and consequently prevented the activation of detoxifying/antioxidant enzymes, ultimately resulting in the generation of sustained oxidative stress. Activating Nrf2 translocation restored redox homeostasis and reversed vulnerability to depression. This mechanism was confirmed in Nrf2-null mice. The mice displayed high levels of oxidative stress and were inherently vulnerable to depression, but this phenotype was reversed by treatment with antioxidants. Our data reveal a novel role for BDNF in controlling redox homeostasis and provide a mechanistic explanation for post-stress vulnerability to depression while suggesting ways to reverse it. Because numerous enzymatic reactions produce reactive oxygen species that must then be cleared, the finding that BDNF controls endogenous redox homeostasis opens new avenues for investigation.
Indexed as
Identifiers
What OpenQuestion holds
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.