ArticleProceedings of the National Academy of Sciences of the United States of America2020
Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 50 citations in OpenAlex.
- Celastrol Ameliorates Vincristine-induced Neuropathic Pain by Inhibiting Spinal Astrocyte Hyperactivation-mediated Inflammation, Oxidative Stress, and Apoptosis.Current neuropharmacology · 2026Article
- Non-human primate seasonal transcriptome atlas reveals seasonal changes in physiology and diseases.Nature communications · 2025Article
- Phytochemicals Targeting BDNF Signaling for Treating Neurological Disorders.Brain sciences · 2025Review
- Why humans evolved blue eyes.Frontiers in psychology · 2025Article
- Targeted Delivery of Celastrol by GA-Modified Liposomal Calcium Carbonate Nanoparticles to Enhance Antitumor Efficacy Against Breast Cancer.Pharmaceutics · 2024Article
- Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation.Frontiers in pharmacology · 2024Article
- A transcriptional program underlying the circannual rhythms of gonadal development in medaka.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Self-immolative nanocapsules precisely regulate depressive neuronal microenvironment for synergistic antidepression therapy.Journal of nanobiotechnology · 2023Article
- Variation in responses to photoperiods and temperatures in Japanese medaka from different latitudes.Zoological letters · 2023Article
- The Nrf2 Pathway in Depressive Disorders: A Systematic Review of Animal and Human Studies.Antioxidants (Basel, Switzerland) · 2023Review
- Celastrol targeting Nedd4 reduces Nrf2-mediated oxidative stress in astrocytes after ischemic stroke.Journal of pharmaceutical analysis · 2023Article
- Developmental impacts of Nrf2 activation by dimethyl fumarate (DMF) in the developing zebrafish (Danio rerio) embryo.Free radical biology & medicine · 2023Article
- Nrf2 Alleviates Cognitive Dysfunction and Brain Inflammatory Injury via Mediating Wfs1 in Rats with Depression-Like Behaviors.Inflammation · 2022Article
- The treatment of depression - searching for new ideas.Frontiers in pharmacology · 2022Review
- Photoperiodic Changes in Both Hypothalamus Neurotransmitters and Circulating Gonadal Steroids Metabolomic Profiles in Relation to Seasonal Reproduction in Male Quail.Frontiers in physiology · 2022Article
- Article
- Strain-Specific Liver Metabolite Profiles in Medaka.Metabolites · 2021Article
- The regulation of animal behavior by cellular stress responses.Experimental cell research · 2021Review
- The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches.Molecules (Basel, Switzerland) · 2021Review
- Activation of BDNF by transcription factor Nrf2 contributes to antidepressant-like actions in rodents.Translational psychiatry · 2021Article
Corrections and comments
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an
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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.