ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Hippocampal neuronal nitric oxide synthase mediates the stress-related depressive behaviors of glucocorticoids by downregulating glucocorticoid receptor.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. 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 70 papers.
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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
70 citing papers in PubMed, 144 citations in OpenAlex.
- Article
- Stress Biology in Cancer: Neuroendocrine-Immune Mechanisms Linking Tumor Progression to Translational Interventions.Cancer communications (London, England) · 2026Review
- The Bidirectional Relationship Between Myocardial Infarction and Depression: Risk Factors, Mechanisms, and Interventions.Biomedicines · 2025Review
- Brain nitric oxide and inflammation in chronic intermittent hypoxia: Contributors to cognitive impairment and hypertension.Brain, behavior, & immunity - health · 2025Review
- nNOS-expressing neurons in the mPFC mediate depression-related behaviors in mice through pPVT-mPFC projections.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- park+/+ and park-/- Drosophila have sexually dimorphic brain redox chemistry.Disease models & mechanisms · 2025Article
- The Interplay of Chronic Stress and Cancer: Pathophysiology and Implications for Integrated Care.Cancer reports (Hoboken, N.J.) · 2025Review
- The Role of the Urea Cycle in the Alzheimer's Disease Brain.Journal of neurochemistry · 2025Review
- Overcrowding Stress in Livestock Production Alters Gut Microbiota Composition and Neuronal Nitric Oxide Synthase (nNOS) Expression in nNOS-HiBiT Knock-in Mouse Model.Food science of animal resources · 2025Article
- Oxidative and nitrosative stress in bipolar affective disorder and its familial aggregation.Indian journal of psychiatry · 2025Article
- Inhibition of prefrontal cortex parvalbumin interneurons mitigates behavioral and physiological sequelae of chronic stress in male mice.Stress (Amsterdam, Netherlands) · 2024Article
- Inhibition of Nitric Oxide Synthesis Prevents the Effects of Intermittent Social Defeat on Cocaine-Induced Conditioned Place Preference in Male Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Emerging roles of SIRT1 activator, SRT2104, in disease treatment.Scientific reports · 2024Review
- Antidepressant-like effects of psychedelics in a chronic despair mouse model: is the 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.Stroke and vascular neurology · 2023Article
- "NO" Time in Fear Response: Possible Implication of Nitric-Oxide-Related Mechanisms in PTSD.Molecules (Basel, Switzerland) · 2023Review
- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety.Neuroscience bulletin · 2023Review
- Ouabain Reverts CUS-Induced Disruption of the HPA Axis and Avoids Long-Term Spatial Memory Deficits.Biomedicines · 2023Article
- Prenatal stress modulates HPA axis homeostasis of offspring through dentate TERT independently of glucocorticoids receptor.Molecular psychiatry · 2023Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanisms underlying the behavioral effects of glucocorticoids are poorly understood. We report here that hippocampal neuronal nitric oxide synthase (nNOS) is a crucial mediator. Chronic mild stress and glucocorticoids exposures caused hippocampal nNOS overexpression via activating mineralocorticoid receptor. In turn, hippocampal nNOS-derived nitric oxide (NO) significantly downregulated local glucocorticoid receptor expression through both soluble guanylate cyclase (sGC)/cGMP and peroxynitrite (ONOO(-))/extracellular signal-regulated kinase signal pathways, and therefore elevated hypothalamic corticotrophin-releasing factor, a peptide that governs the hypothalamic-pituitary-adrenal axis. More importantly, nNOS deletion or intrahippocampal nNOS inhibition and NO-cGMP signaling blockade (using NO scavenger or sGC inhibitor) prevented the corticosterone-induced behavioral modifications, suggesting that hippocampal nNOS is necessary for the role of glucocorticoids in mediating depressive behaviors. In addition, directly delivering ONOO(-) donor into hippocampus caused depressive-like behaviors. Our findings reveal a role of hippocampal nNOS in regulating the behavioral effects of glucocorticoids.
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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.