ArticleTranslational psychiatry2021
Synergistic inhibition of histone modifiers produces therapeutic effects in adult Shank3-deficient mice.
Article in Translational psychiatry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Tryptophan modulation in individuals with attention deficit hyperactivity disorder: a systematic review.Journal of neural transmission (Vienna, Austria : 1996) · 2022Pooled it
- Opposing Patterns of the Histone Variant MacroH2A1.1 in Fmr1 Knockout and BTBR T+ Itpr3tf/J Mouse Models of Autism Spectrum Disorder.Molecular neurobiology · 2026Article
- Early postnatal dysfunction of ACC PV interneurons in Shank3BMolecular psychiatry · 2025Article
- Emerging Epigenetic Therapeutics and Diagnostics for Autism Spectrum Disorder.Current issues in molecular biology · 2025Review
- Phenotype and psychometric characterization of Phelan-McDermid syndrome patients: pioneering towards personalized medicine.Frontiers in psychiatry · 2025Article
- The Use of Nutraceutical and Pharmacological Strategies in Murine Models of Autism Spectrum Disorder.Cells · 2024Review
- A snapshot on introspection of autism spectrum disorder.Molecular biology reports · 2024Review
- Systemic histone deacetylase inhibition ameliorates the aberrant responses to acute stress in socially isolated male mice.The Journal of physiology · 2024Article
- A mouse model of ATRX deficiency with cognitive deficits and autistic traits.Journal of neurodevelopmental disorders · 2023Article
- Autism Spectrum Disorder: Neurodevelopmental Risk Factors, Biological Mechanism, and Precision Therapy.International journal of molecular sciences · 2023Review
- Histone Deacetylase Inhibition Restores Behavioral and Synaptic Function in a Mouse Model of 16p11.2 Deletion.The international journal of neuropsychopharmacology · 2022Article
- Insulin-like growth factor 1 regulates excitatory synaptic transmission in pyramidal neurons from adult prefrontal cortex.Neuropharmacology · 2022Article
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- Rescue of histone hypoacetylation and social deficits by ketogenic diet in a Shank3 mouse model of autism.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Comparison of SHANK3 deficiency in animal models: phenotypes, treatment strategies, and translational implications.Journal of neurodevelopmental disorders · 2021Review
- Early Chronic Memantine Treatment-Induced Transcriptomic Changes in Wild-Type andFrontiers in molecular neuroscience · 2021Article
- Gene Dosage- and Age-Dependent Differential Transcriptomic Changes in the Prefrontal Cortex ofFrontiers in molecular neuroscience · 2021Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Autism spectrum disorder (ASD) is a lifelong developmental disorder characterized by social deficits and other behavioral abnormalities. Dysregulation of epigenetic processes, such as histone modifications and chromatin remodeling, have been implicated in ASD pathology, and provides a promising therapeutic target for ASD. Haploinsufficiency of the SHANK3 gene is causally linked to ASD, so adult (3-5 months old) Shank3-deficient male mice were used in this drug discovery study. We found that combined administration of the class I histone deacetylase inhibitor Romidepsin and the histone demethylase LSD1 inhibitor GSK-LSD1 persistently ameliorated the autism-like social preference deficits, while each individual drug alone was largely ineffective. Another behavioral abnormality in adult Shank3-deficient male mice, heightened aggression, was also alleviated by administration of the dual drugs. Furthermore, Romidepsin/GSK-LSD1 treatment significantly increased transcriptional levels of NMDA receptor subunits in prefrontal cortex (PFC) of adult Shank3-deficient mice, resulting in elevated synaptic expression of NMDA receptors and the restoration of NMDAR synaptic function in PFC pyramidal neurons. These results have offered a novel pharmacological intervention strategy for ASD beyond early developmental periods.
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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.