ArticleMolecular psychiatry2015
Neurotrophic factor-α1 prevents stress-induced depression through enhancement of neurogenesis and is activated by rosiglitazone.
Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Neuronal Stem Cell and Drug Interactions: A Systematic Review and Meta-Analysis: Concise Review.Stem cells translational medicine · 2019Pooled it
- Rosiglitazone Adjunct to Sertraline for Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Trial.Depression and anxiety · 2026Trial
- Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.Malaria journal · 2017Trial
- Fibroblast Growth Factors and Their Receptors in Major Depressive Disorder: A Scoping Review of Translational Research.International journal of molecular sciences · 2026Article
- Carboxypeptidase E Alleviates Depressive-Like Behaviors in Mice by Regulating BDNF/Nrf2 Axis-Mediated Ferroptosis.Neurochemical research · 2026Article
- The Mechanism of Carboxypeptidase E Regulating NLRP3 Inflammasome Signaling in the Pathogenesis of Depression-Like Behaviors in Mice.Neuroimmunomodulation · 2026Article
- Selecting an appropriate stress model of depression in rodents.World journal of psychiatry · 2025Review
- Antidepressant effects of ershiwei roudoukou pills and its active ingredient Macelignan: Multiple mechanisms involving oxidative stress, neuroinflammation and synaptic plasticity.Translational psychiatry · 2025Article
- Deficiency of fibroblast growth factor 2 promotes contractile phenotype of pericytes in ascending thoracic aortic aneurysm.American journal of physiology. Heart and circulatory physiology · 2025Article
- The Mechanism of HDAC2 Inhibitors on Chronic Pancreatitis Pain.Journal of neurological surgery reports · 2025Article
- Neurotrophic factor alpha 1 gene therapy in Alzheimer's disease: scope and advancements.Frontiers in molecular neuroscience · 2025Review
- Neuritin Controls Axonal Branching in Serotonin Neurons: A Possible Mediator Involved in the Regulation of Depressive and Anxiety Behaviors via FGF Signaling.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Exploring the molecular mechanisms of PPARγ agonists in modulating memory impairment in neurodegenerative disorders.Molecular biology reports · 2024Review
- Article
- Agomirs upregulating carboxypeptidase E expression rescue hippocampal neurogenesis and memory deficits in Alzheimer's disease.Translational neurodegeneration · 2024Article
- Converged avenues: depression and Alzheimer's disease- shared pathophysiology and novel therapeutics.Molecular biology reports · 2024Review
- Carboxypeptidase E conditional knockout mice exhibit learning and memory deficits and neurodegeneration.Translational psychiatry · 2023Article
- Restoring carboxypeptidase E rescues BDNF maturation and neurogenesis in aged brains.Life medicine · 2023Article
- Anti-depressant-like effects of rannasangpei and its active ingredient crocin-1 on chronic unpredictable mild stress mice.Frontiers in pharmacology · 2023Article
- Blood-Brain Barrier Dysfunction in the Pathogenesis of Major Depressive Disorder.Cellular and molecular neurobiology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Major depressive disorder is often linked to stress. Although short-term stress is without effect in mice, prolonged stress leads to depressive-like behavior, indicating that an allostatic mechanism exists in this difference. Here we demonstrate that mice after short-term (1 h per day for 7 days) chronic restraint stress (CRS), do not display depressive-like behavior. Analysis of the hippocampus of these mice showed increased levels of neurotrophic factor-α1 (NF-α1; also known as carboxypeptidase E, CPE), concomitant with enhanced fibroblast growth factor 2 (FGF2) expression, and an increase in neurogenesis in the dentate gyrus. In contrast, after prolonged (6 h per day for 21 days) CRS, mice show decreased hippocampal NF-α1 and FGF2 levels and depressive-like responses. In NF-α1-knockout mice, hippocampal FGF2 levels and neurogenesis are reduced. These mice exhibit depressive-like behavior that is reversed by FGF2 administration. Indeed, studies in cultured hippocampal neurons reveal that NF-α1 treatment directly upregulates FGF2 expression through extracellular signal-regulated kinase-Sp1 signaling. Thus, during short-term CRS, hippocampal NF-α1 expression is upregulated and has a key role in preventing the onset of depressive-like behavior through enhanced FGF2-mediated neurogenesis. To evaluate the therapeutic potential of this pathway, we examined, rosiglitazone (Rosi), a PPARγ agonist, which has been shown to have antidepressant activity in rodents and humans. Rosi upregulates FGF2 expression in a NF-α1-dependent manner in hippocampal neurons. Mice fed Rosi show increased hippocampal NF-α1 levels and neurogenesis compared with controls, thereby indicating the antidepressant action of this drug. Development of drugs that activate the NF-α1/FGF2/neurogenesis pathway can offer a new approach to depression therapy.
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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.