ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
PDE-4 inhibition rescues aberrant synaptic plasticity in Drosophila and mouse models of fragile X syndrome.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 55 citations in OpenAlex.
- Inhibition of phosphodiesterase-4D in adults with fragile X syndrome: a randomized, placebo-controlled, phase 2 clinical trial.Nature medicine · 2021Trial
- The Emerging Role of Phosphodiesterase Inhibitors in Fragile X Syndrome and Autism Spectrum Disorder.Pharmaceuticals (Basel, Switzerland) · 2025Review
- From Discovery to Innovative Translational Approaches in 80 Years of Fragile X Syndrome Research.Biomedicines · 2025Review
- How close are we to a cAMP- and cGMP-theory-based pharmacological therapy for fragile X syndrome?Cell reports. Medicine · 2025Article
- Connecting dots: Preclinical foundations to clinical realities of PDE4 inhibitors in Alzheimer's disease.Inflammopharmacology · 2025Review
- An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs.Nature communications · 2024Article
- State-of-the-art therapies for fragile X syndrome.Developmental medicine and child neurology · 2024Review
- A novel combination treatment for fragile X syndrome predicted using computational methods.Brain communications · 2024Article
- Phosphodiesterase 4D activity in acrodysostosis-associated neural pathology: too much or too little?Brain communications · 2024Review
- Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.Frontiers in psychiatry · 2024Review
- Article
- Targeted Treatments for Fragile X Syndrome.Advances in neurobiology · 2023Article
- Review
- Phosphodiesterase 2A inhibition corrects the aberrant behavioral traits observed in genetic and environmental preclinical models of Autism Spectrum Disorder.Translational psychiatry · 2022Article
- Fragile X Syndrome: From Molecular Aspect to Clinical Treatment.International journal of molecular sciences · 2022Review
- Autism Symptoms in Children and Young Adults With Fragile X Syndrome, Angelman Syndrome, Tuberous Sclerosis Complex, and Neurofibromatosis Type 1: A Cross-Syndrome Comparison.Frontiers in psychiatry · 2022Article
- Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders.Molecular psychiatry · 2021Review
- The PDE10A Inhibitor TAK-063 Reverses Sound-Evoked EEG Abnormalities in a Mouse Model of Fragile X Syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Article
- The Use of Peptides in the Treatment of Fragile X Syndrome: Challenges and Opportunities.Frontiers in psychiatry · 2021Article
- Fragile X Mental Retardation Protein positively regulates PKA anchor Rugose and PKA activity to control actin assembly in learning/memory circuitry.Neurobiology of disease · 2019Article
Corrections and comments
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Authors and funding
25 authors at 6 institutions in 2 countries.
Funding
Abstract
Fragile X syndrome (FXS) is the leading cause of both intellectual disability and autism resulting from a single gene mutation. Previously, we characterized cognitive impairments and brain structural defects in a Drosophila model of FXS and demonstrated that these impairments were rescued by treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium. A well-documented biochemical defect observed in fly and mouse FXS models and FXS patients is low cAMP levels. cAMP levels can be regulated by mGluR signaling. Herein, we demonstrate PDE-4 inhibition as a therapeutic strategy to ameliorate memory impairments and brain structural defects in the Drosophila model of fragile X. Furthermore, we examine the effects of PDE-4 inhibition by pharmacologic treatment in the fragile X mouse model. We demonstrate that acute inhibition of PDE-4 by pharmacologic treatment in hippocampal slices rescues the enhanced mGluR-dependent LTD phenotype observed in FXS mice. Additionally, we find that chronic treatment of FXS model mice, in adulthood, also restores the level of mGluR-dependent LTD to that observed in wild-type animals. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of FXS is an important advance, in that this identifies and validates PDE-4 inhibition as potential therapeutic intervention for the treatment of individuals afflicted with FXS.
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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.