ArticleScientific reports2017
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype.
Article in Scientific reports, 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 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Alterations of microRNAs across human and mouse limbic brain areas: molecular mechanisms and biological processes involved in major depressive disorder.Neurobiology of stress · 2026Article
- The Eph-ephrin system in neuropsychiatric and neurodevelopmental disorders.Journal of psychiatry & neuroscience : JPN · 2026Review
- The role of Ephexin1 in translation and mTOR-targeted cancer therapy.Experimental & molecular medicine · 2025Article
- Master regulators of neurogenesis: the dynamic roles of Ephrin receptors across diverse cellular niches.Translational psychiatry · 2024Review
- Article
- Repurposing Ketamine in the Therapy of Depression and Depression-Related Disorders: Recent Advances and Future Potential.Aging and disease · 2024Review
- Lipidation and PEGylation Strategies to Prolong theEuropean journal of medicinal chemistry · 2023Article
- Probing pathways by which rhynchophylline modifies sleep using spatial transcriptomics.Biology direct · 2023Article
- Awakening the dormant: Role of axonal guidance cues in stress-induced reorganization of the adult prefrontal cortex leading to depression-like behavior.Frontiers in neural circuits · 2023Review
- Sleep-inducing effect of Rhynchophylline inSleep advances : a journal of the Sleep Research Society · 2023Article
- Downregulation of CRTC1 Is Involved in CUMS-Induced Depression-Like Behavior in the Hippocampus and Its RNA Sequencing Analysis.Molecular neurobiology · 2022Article
- The Eph receptor A4 plays a role in demyelination and depression-related behavior.The Journal of clinical investigation · 2022Article
- Nuclear factor of activated T cells 4 in the prefrontal cortex is required for prophylactic actions of (R)-ketamine.Translational psychiatry · 2022Article
- Dissecting indirect genetic effects from peers in laboratory mice.Genome biology · 2021Article
- Cellular Effects of Rhynchophylline and Relevance to Sleep Regulation.Clocks & sleep · 2021Review
- Double inhibition and activation mechanisms of Ephexin family RhoGEFs.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Integrating Clinical and Genomic Analyses of Hippocampal-Prefrontal Circuit Disorder in Depression.Frontiers in genetics · 2020Article
- EphA4 loss improves social memory performance and alters dendritic spine morphology without changes in amyloid pathology in a mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2019Article
- Review
- Keap1-Nrf2 signaling pathway confers resilience versus susceptibility to inescapable electric stress.European archives of psychiatry and clinical neuroscience · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4-ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effect of EphA4 inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the nucleus accumbens (NAc), of susceptible mice after social defeat stress. Furthermore, the p-EphA4/EphA4 ratio was higher in the parietal cortex of depressed patients compared with controls. Systemic administration of rhynchophylline, produced a rapid antidepressant-like effect in a social defeat stress model by inhibiting EphA4-ephexin1 signaling and activating brain-derived neurotrophic factor-TrkB signaling in the PFC and hippocampus. Pretreatment with rhynchophylline before each social defeat stress could prevent the onset of the depression-like phenotype after repeated social defeat stress. Overexpression of EphA4 in the medial PFC owing to infection with an EphA4 adeno-associated virus caused the depression-like phenotype 3 weeks later and rhynchophylline had a rapid antidepressant-like effect in these mice. These findings suggest that increased EphA4-ephexin1 signaling in the PFC plays a role in the pathophysiology of depression.
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