ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
NADPH oxidase mediates depressive behavior induced by chronic stress in mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83 citing papers in PubMed, 184 citations in OpenAlex.
- Fabrication and efficacy evaluation of scopolamine-loaded dissolving microneedle for rapid antidepressant therapy.International journal of pharmaceutics: X · 2026Article
- Neurovascular coupling in the basolateral amygdala modulates negative emotions.Cell research · 2026Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Differential behavior responses and genetic alteration underpinning exercise effectiveness in stress-susceptible mice.Scientific reports · 2025Article
- Running Reverses Chronic Stress-Induced Changes in Serotonergic Modulation of Hippocampal Granule Cells and Altered Behavioural Responses.The European journal of neuroscience · 2025Article
- Hyperactivity in male and female mice manifests differently following early, acute prenatal alcohol exposure and mild juvenile stress.Frontiers in behavioral neuroscience · 2025Article
- The influence of exercise intensity on comorbid anxious behavior in psychiatric conditions.The journal of physiological sciences : JPS · 2024Article
- Lipopolysaccharide binding protein resists hepatic oxidative stress by regulating lipid droplet homeostasis.Nature communications · 2024Article
- Article
- Depression and the Glutamate/GABA-Glutamine Cycle.Current neuropharmacology · 2024Review
- Higher serum ascorbic acid levels are associated with lower depression prevalence in US adults: a case-control study.Frontiers in nutrition · 2024Article
- Chronic stress-induced anxiety-like behavior, hippocampal oxidative, and endoplasmic reticulum stress are reversed by young plasma transfusion in aged adult rats.Iranian journal of basic medical sciences · 2024Article
- Therapeutic potential of NOX inhibitors in neuropsychiatric disorders.Psychopharmacology · 2023Review
- Flavonols in Action: Targeting Oxidative Stress and Neuroinflammation in Major Depressive Disorder.International journal of molecular sciences · 2023Review
- Review
- Understanding the Role of Oxidative Stress, Neuroinflammation and Abnormal Myelination in Excessive Aggression Associated with Depression: Recent Input from Mechanistic Studies.International journal of molecular sciences · 2023Review
- A tau fragment links depressive-like behaviors and cognitive declines in Alzheimer's disease mouse models through attenuating mitochondrial function.Frontiers in aging neuroscience · 2023Article
- Article
- Extracellular Vesicles from Gram-positive and Gram-negative Probiotics Remediate Stress-Induced Depressive Behavior in Mice.Molecular neurobiology · 2022Article
- Review
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress is a potent risk factor for depression, yet the underlying mechanism is not clearly understood. In the present study, we explored the mechanism of development and maintenance of depression in a stress-induced animal model. Mice restrained for 2 h daily for 14 d showed distinct depressive behavior, and the altered behavior persisted for >3 months in the absence of intervention. Acute restraint induced a surge of oxidative stress in the brain, and stress-induced oxidative stress progressively increased with repetition of stress. In vitro, the stress hormone glucocorticoid generated superoxide via upregulation of NADPH oxidase. Consistently, repeated restraints increased the expression of the key subunits of NADPH oxidase, p47phox and p67phox, in the brain. Moreover, stressed brains markedly upregulated the expression of p47phox to weak restress evoked in the poststress period, and this molecular response was reminiscent of amplified ROS surge to restress. Pharmacological inhibition of NADPH oxidase by the NADPH oxidase inhibitor apocynin during the stress or poststress period completely blocked depressive behavior. Consistently, heterozygous p47phox knock-out mice (p47phox(+/-)) or molecular inhibition of p47phox with Lenti shRNA-p47phox in the hippocampus suppressed depressive behavior. These results suggest that repeated stress promotes depressive behavior through the upregulation of NADPH oxidase and the resultant metabolic oxidative stress, and that the inhibition of NADPH oxidase provides beneficial antidepression effects.
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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.