ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Glucocorticoid-related molecular signaling pathways regulating hippocampal neurogenesis.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 3 of them syntheses that pooled it.
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Who cites it
153 citing papers in PubMed, 3 syntheses or guidelines pooled it, 313 citations in OpenAlex.
- From placenta to the foetus: a systematic review of in vitro models of stress- and inflammation-induced depression in pregnancy.Molecular psychiatry · 2025Pooled it
- Acute and long-term effects of adolescence stress exposure on rodent adult hippocampal neurogenesis, cognition, and behaviour.Molecular psychiatry · 2023Pooled it
- Spousal caregiving, widowhood, and cognition: A systematic review and a biopsychosocial framework for understanding the relationship between interpersonal losses and dementia risk in older adulthood.Neuroscience and biobehavioral reviews · 2022Pooled it
- Omega-3 polyunsaturated fatty acids protect against inflammation through production of LOX and CYP450 lipid mediators: relevance for major depression and for human hippocampal neurogenesis.Molecular psychiatry · 2021Trial
- Absolute Measurements of Macrophage Migration Inhibitory Factor and Interleukin-1-β mRNA Levels Accurately Predict Treatment Response in Depressed Patients.The international journal of neuropsychopharmacology · 2016Trial
- The Effect of Propofol Versus Isoflurane Anesthesia on Human Cerebrospinal Fluid Markers of Alzheimer's Disease: Results of a Randomized Trial.Journal of Alzheimer's disease : JAD · 2016Trial
- Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Reconciling the neurogenic hypothesis of depression with recent advances in adult hippocampal neurogenesis research in humans.Molecular psychiatry · 2026Review
- Fatigue after COVID-19 infection is associated with peripheral immunometabolic alterations affecting neuroimmune responses in the hippocampus.Translational psychiatry · 2026Article
- Mice produce interneurons in the septum as a response to aversive experiences and antidepressant treatment.Science advances · 2026Article
- Comparative Multiomics Analysis of Cerebral Organoid-Derived Exosomes during Organoid Maturation.Nano letters · 2026Article
- Inhibiting glucocorticoid receptors enhances adult spinal cord neural stem cell activity and improves outcomes in spinal cord injury.Communications biology · 2026Article
- Inhibition of stress resilience and adult hippocampal neurogenesis by platelet-derived LPA16:0 in anxiety.Nature communications · 2026Article
- Glucocorticoids and cell fate in the developing brain: Neuroendocrine mechanisms shaping developmental trajectories.Journal of neuroendocrinology · 2026Review
- Associations among stress perception, clinical symptoms, and hippocampal subfield volumes in first-episode patients with schizophrenia.Frontiers in psychiatry · 2026Article
- The dietary ligands, omega-3 fatty acid endocannabinoids and short-chain fatty acids prevent cytokine-induced reduction of human hippocampal neurogenesis and alter the expression of genes involved in neuroinflammation and neuroplasticity.Molecular psychiatry · 2025Article
- Selective Hippocampal Subfield Atrophy Mediates Cognitive Decline in Cushing's Disease.Brain and behavior · 2025Article
- The Etiological Role of Impaired Neurogenesis in Schizophrenia: Interactions with Inflammatory, Microbiome and Hormonal Signaling.International journal of molecular sciences · 2025Review
- Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence.International journal of molecular sciences · 2025Review
- Kruppel-like factor 9 may regulate the inflammatory injury of chondrocytes by affecting NF-κB signaling.Journal of orthopaedic surgery and research · 2025Article
93 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 9 institutions in 3 countries.
Funding
Abstract
Stress and glucocorticoid hormones regulate hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. We, therefore, investigated the molecular signaling pathways mediating the effects of cortisol on proliferation, neuronal differentiation, and astrogliogenesis, in an immortalized human hippocampal progenitor cell line. In addition, we examined the molecular signaling pathways activated in the hippocampus of prenatally stressed rats, characterized by persistently elevated glucocorticoid levels in adulthood. In human hippocampal progenitor cells, we found that low concentrations of cortisol (100 nM) increased proliferation (+16%), decreased neurogenesis into microtubule-associated protein 2 (MAP2)-positive neurons (-24%) and doublecortin (Dcx)-positive neuroblasts (-21%), and increased differentiation into S100β-positive astrocytes (+23%). These effects were dependent on the mineralocorticoid receptor (MR) as they were abolished by the MR antagonist, spironolactone, and mimicked by the MR-agonist, aldosterone. In contrast, high concentrations of cortisol (100 μM) decreased proliferation (-17%) and neuronal differentiation into MAP2-positive neurons (-22%) and into Dcx-positive neuroblasts (-27%), without regulating astrogliogenesis. These effects were dependent on the glucocorticoid receptor (GR), blocked by the GR antagonist RU486, and mimicked by the GR-agonist, dexamethasone. Gene expression microarray and pathway analysis showed that the low concentration of cortisol enhances Notch/Hes-signaling, the high concentration inhibits TGFβ-SMAD2/3-signaling, and both concentrations inhibit Hedgehog signaling. Mechanistically, we show that reduced Hedgehog signaling indeed critically contributes to the cortisol-induced reduction in neuronal differentiation. Accordingly, TGFβ-SMAD2/3 and Hedgehog signaling were also inhibited in the hippocampus of adult prenatally stressed rats with high glucocorticoid levels. In conclusion, our data demonstrate novel molecular signaling pathways that are regulated by glucocorticoids in vitro, in human hippocampal progenitor cells, and by stress in vivo, in the rat hippocampus.
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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.