ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
HDAC6 regulates glucocorticoid receptor signaling in serotonin pathways with critical impact on stress resilience.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 143 citations in OpenAlex.
- Epigenetic Control of Stress-Induced Depression: Emerging Roles of HDAC3 and HDAC6.International journal of molecular sciences · 2026Review
- Pharmacological Inhibition of HDAC6 Transiently Reduces Voluntary Ethanol Consumption in Male Mice.Alcohol, clinical & experimental research · 2026Article
- Unraveling the enigma: Post-translational modifications in psychiatric disorders and their regulatory mechanisms.Journal of translational internal medicine · 2026Article
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- HDAC6 Inhibition Drives Synaptic Protein Acetylation and Enhances Long-Term Memory in Mice.Molecular neurobiology · 2025Article
- PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD.Molecular psychiatry · 2025Article
- Assessment of test-retest reproducibility by [EJNMMI research · 2025Article
- Review
- Rapid and sustained antidepressant effects of tubastatin A in a mouse model of depression.Scientific reports · 2025Article
- Early life stress and functional connectivity in antipsychotic-naïve first episode psychosis patients.Schizophrenia (Heidelberg, Germany) · 2025Article
- Epigenetic mechanisms of rapid-acting antidepressants.Translational psychiatry · 2024Review
- The role of epigenetics in anxiety disorders.Molecular biology reports · 2023Review
- HDAC6 Deficiency Has Moderate Effects on Behaviors and Parkinson's Disease Pathology in Mice.International journal of molecular sciences · 2023Article
- Prenatal Hypoxia-Induced Adverse Reaction to Mild Stress is Associated with Depressive-Like Changes in the Glucocorticoid System of Rats.Neurochemical research · 2023Article
- Male histone deacetylase 6 (HDAC6) knockout mice have enhanced ventilatory responses to hypoxic challenge.Frontiers in physiology · 2023Article
- Involvement of brain cell phenotypes in stress-vulnerability and resilience.Frontiers in neuroscience · 2023Review
- A Role for Histone Deacetylases in the Biology and Treatment of Post-Traumatic Stress Disorder: What Do We Know and Where Do We Go from Here?Complex psychiatry · 2022Review
- Discovery of Benzylpiperazine Derivatives as CNS-Penetrant and Selective Histone Deacetylase 6 Inhibitors.ACS medicinal chemistry letters · 2022Article
- Resilience to the effects of social stress on vulnerability to developing drug addiction.World journal of psychiatry · 2022Review
- Corticosterone-mediated regulation and functions of miR-218-5p in rat brain.Scientific reports · 2022Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Genetic variations in certain components of the glucocorticoid receptor (GR) chaperone complex have been associated with the development of stress-related affective disorders and individual variability in therapeutic responses to antidepressants. Mechanisms that link GR chaperoning and stress susceptibility are not well understood. Here, we show that the effects of glucocorticoid hormones on socioaffective behaviors are critically regulated via reversible acetylation of Hsp90, a key component of the GR chaperone complex. We provide pharmacological and genetic evidence indicating that the cytoplasmic lysine deacetylase HDAC6 controls Hsp90 acetylation in the brain, and thereby modulates Hsp90-GR protein-protein interactions, as well as hormone- and stress-induced GR translocation, with a critical impact on GR downstream signaling and behavior. Pet1-Cre-driven deletion of HDAC6 in serotonin neurons, the densest HDAC6-expressing cell group in the mouse brain, dramatically reduced acute anxiogenic effects of the glucocorticoid hormone corticosterone in the open-field, elevated plus maze, and social interaction tests. Serotonin-selective depletion of HDAC6 also blocked the expression of social avoidance in mice exposed to chronic social defeat and concurrently prevented the electrophysiological and morphological changes induced, in serotonin neurons, by this murine model of traumatic stress. Together, these results identify HDAC6 inhibition as a potential new strategy for proresilience and antidepressant interventions through regulation of the Hsp90-GR heterocomplex and focal prevention of GR signaling in serotonin pathways. Our data thus uncover an alternate mechanism by which pan-HDAC inhibitors may regulate stress-related behaviors independently of their action on histones.
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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.