ArticleTranslational psychiatry2016
Anxiety and depression with neurogenesis defects in exchange protein directly activated by cAMP 2-deficient mice are ameliorated by a selective serotonin reuptake inhibitor, Prozac.
Article in Translational psychiatry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.
- Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.European journal of clinical pharmacology · 2024Pooled it
- Pathophysiological roles of neural stem cells in neuropsychiatric diseases: from plasticity to pharmacological targeting.Acta pharmacologica Sinica · 2026Review
- G-protein coupled receptor kinase 2 mediates rheumatoid arthritis-induced depression-like behaviors via the hippocampal CRHR1 signaling pathway.Acta pharmacologica Sinica · 2025Article
- Narrating the psychoneuroimmunomodulatory properties of serotonin 5-HTActa neuropsychiatrica · 2025Review
- Trans-ancestry Genome-Wide Analyses in UK Biobank Yield Novel Risk Loci for Major Depression.medRxiv : the preprint server for health sciences · 2025Article
- Fear memory regulation by the cAMP signaling pathway as an index of reexperiencing symptoms in posttraumatic stress disorder.Molecular psychiatry · 2024Article
- Interactions between Ras and Rap signaling pathways during neurodevelopment in health and disease.Frontiers in molecular neuroscience · 2024Review
- Functional Dimerization of Serotonin Receptors: Role in Health and Depressive Disorders.International journal of molecular sciences · 2023Review
- Rolipram Ameliorates Memory Deficits and Depression-Like Behavior in APP/PS1/tau Triple Transgenic Mice: Involvement of Neuroinflammation and Apoptosis via cAMP Signaling.The international journal of neuropsychopharmacology · 2023Article
- The Expression of Epac2 and GluA3 in an Alzheimer's Disease Experimental Model and Postmortem Patient Samples.Biomedicines · 2023Article
- Cannabinoids modulate the microbiota-gut-brain axis in HIV/SIV infection by reducing neuroinflammation and dysbiosis while concurrently elevating endocannabinoid and indole-3-propionate levels.Journal of neuroinflammation · 2023Article
- Article
- Identification of putative genetic variants in major depressive disorder patients in Pakistan.Molecular biology reports · 2022Article
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- Gene polymorphisms of insulin secretion signaling pathway associated with clopidogrel resistance in Han Chinese population.Journal of clinical laboratory analysis · 2021Article
- Epac: new emerging cAMP-binding protein.BMB reports · 2021Review
- Microbiome-Metabolomics Reveals Endogenous Alterations of Energy Metabolism by the Dushen Tang to Attenuate D-Galactose-Induced Memory Impairment in Rats.BioMed research international · 2021Article
- Exchange protein directly activated by cAMP (Epac) 1 plays an essential role in stress-induced exercise capacity by regulating PGC-1α and fatty acid metabolism in skeletal muscle.Pflugers Archiv : European journal of physiology · 2020Article
- Cell-specific expression of Epac2 in the subventricular and subgranular zones.Molecular brain · 2019Article
- Exchange protein directly activated by cAMP 2 is required for corticotropin-releasing hormone-mediated spine loss.The European journal of neuroscience · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellular cAMP and serotonin are important modulators of anxiety and depression. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI) also known as Prozac, is widely used against depression, potentially by activating cAMP response element-binding protein (CREB) and increasing brain-derived neurotrophic factor (BDNF) through protein kinase A (PKA). However, the role of Epac1 and Epac2 (Rap guanine nucleotide exchange factors, RAPGEF3 and RAPGEF4, respectively) as potential downstream targets of SSRI/cAMP in mood regulations is not yet clear. Here, we investigated the phenotypes of Epac1 (Epac1(-/-)) or Epac2 (Epac2(-/-)) knockout mice by comparing them with their wild-type counterparts. Surprisingly, Epac2(-/-) mice exhibited a wide range of mood disorders, including anxiety and depression with learning and memory deficits in contextual and cued fear-conditioning tests without affecting Epac1 expression or PKA activity. Interestingly, rs17746510, one of the three single-nucleotide polymorphisms (SNPs) in RAPGEF4 associated with cognitive decline in Chinese Alzheimer's disease (AD) patients, was significantly correlated with apathy and mood disturbance, whereas no significant association was observed between RAPGEF3 SNPs and the risk of AD or neuropsychiatric inventory scores. To further determine the detailed role of Epac2 in SSRI/serotonin/cAMP-involved mood disorders, we treated Epac2(-/-) mice with a SSRI, Prozac. The alteration in open field behavior and impaired hippocampal cell proliferation in Epac2(-/-) mice were alleviated by Prozac. Taken together, Epac2 gene polymorphism is a putative risk factor for mood disorders in AD patients in part by affecting the hippocampal neurogenesis.
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