ArticleMolecular psychiatry2021
Valproate reverses mania-like behaviors in mice via preferential targeting of HDAC2.
Article in Molecular psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Hypothalamic Oxytocin Neuronal Activation Induces Bipolar-Like Mood Changes in Mice in a Sex- and Dosage-Dependent Manner.Neuroscience bulletin · 2026Article
- Dose-Dependent Neuroprotective Effects of Valproate on Motor Function and Striatal D2 Receptor Stability in a 6-OHDA Rat Model of Parkinson's Disease.International journal of molecular sciences · 2026Article
- Image-based epigenetic profiling with deep learning and high-speed super-resolution microscopy.Epigenetics & chromatin · 2026Article
- Microglia-mediated inflammation and synaptic pruning contribute to sleep deprivation-induced mania in a sex-specific manner.Translational psychiatry · 2025Article
- Epigenetics and Gut Microbiota in the Pathogenesis and Treatment of Bipolar Disorder (BD).Cells · 2025Review
- Linking Mitochondrial Dysfunction, Neurotransmitter, and Neural Network Abnormalities and Mania: Elucidating Neurobiological Mechanisms of the Therapeutic Effect of the Ketogenic Diet in Bipolar Disorder.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2025Review
- Progress and Implications from Genetic Studies of Bipolar Disorder.Neuroscience bulletin · 2024Review
- A widespread electrical brain network encodes anxiety in health and depressive states.bioRxiv : the preprint server for biology · 2024Article
- Valproic acid ameliorates cauda equina injury by suppressing HDAC2-mediated ferroptosis.CNS neuroscience & therapeutics · 2024Article
- Review
- Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia.Journal for immunotherapy of cancer · 2023Article
- Genome-Environment Interactions and Psychiatric Disorders.Biomedicines · 2023Review
- Taking subjectivity seriously: towards a unification of phenomenology, psychiatry, and neuroscience.Molecular psychiatry · 2023Review
- The trilateral interactions between mammalian target of rapamycin (mTOR) signaling, the circadian clock, and psychiatric disorders: an emerging model.Translational psychiatry · 2022Review
- Phenotypes, mechanisms and therapeutics: insights from bipolar disorder GWAS findings.Molecular psychiatry · 2022Review
- Neurobiological and behavioral mechanisms of circadian rhythm disruption in bipolar disorder: A critical multi-disciplinary literature review and agenda for future research from the ISBD task force on chronobiology.Bipolar disorders · 2022Review
- Transcriptional Alterations in Dorsolateral Prefrontal Cortex and Nucleus Accumbens Implicate Neuroinflammation and Synaptic Remodeling in Opioid Use Disorder.Biological psychiatry · 2021Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 2 countries.
Funding
Abstract
Valproate (VPA) has been used in the treatment of bipolar disorder since the 1990s. However, the therapeutic targets of VPA have remained elusive. Here we employ a preclinical model to identify the therapeutic targets of VPA. We find compounds that inhibit histone deacetylase proteins (HDACs) are effective in normalizing manic-like behavior, and that class I HDACs (e.g., HDAC1 and HDAC2) are most important in this response. Using an RNAi approach, we find that HDAC2, but not HDAC1, inhibition in the ventral tegmental area (VTA) is sufficient to normalize behavior. Furthermore, HDAC2 overexpression in the VTA prevents the actions of VPA. We used RNA sequencing in both mice and human induced pluripotent stem cells (iPSCs) derived from bipolar patients to further identify important molecular targets. Together, these studies identify HDAC2 and downstream targets for the development of novel therapeutics for bipolar mania.
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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.