ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Learning and memory deficits consequent to reduction of the fragile X mental retardation protein result from metabotropic glutamate receptor-mediated inhibition of cAMP signaling in Drosophila.
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 49 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Pooled it
- ROC Analysis of Biomarker Combinations in Fragile X Syndrome-Specific Clinical Trials: Evaluating Treatment Efficacy via Exploratory Biomarkers.Translational psychiatry · 2025Trial
- 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
- Article
- Mechanistic insights into cadmium-related premature aging inFrontiers in neuroscience · 2025Article
- An experimentally validated approach to automated biological evidence generation in drug discovery using knowledge graphs.Nature communications · 2024Article
- Research progress on phosphodiesterase 4 inhibitors in central nervous system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Modeling neurodegenerative and neurodevelopmental disorders in theLearning & memory (Cold Spring Harbor, N.Y.) · 2024Review
- Altered brain serotonin 5-HTNeuropharmacology · 2024Article
- A novel combination treatment for fragile X syndrome predicted using computational methods.Brain communications · 2024Article
- Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024Review
- Combinatory Actions of Co-transmitters in Dopaminergic Systems ModulateThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Increased body weight in mice with fragile X messenger ribonucleoprotein 1 (Fmr1) gene mutation is associated with hypothalamic dysfunction.Scientific reports · 2023Article
- Associative Learning Requires Neurofibromin to Modulate GABAergic Inputs to Drosophila Mushroom Bodies.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Rett Syndrome and Fragile X Syndrome: Different Etiology With Common Molecular Dysfunctions.Frontiers in cellular neuroscience · 2021Review
- Phenotypic Trade-Offs: Deciphering the Impact of Neurodiversity on Drug Development in Fragile X Syndrome.Frontiers in psychiatry · 2021Article
- Genetic background mutations drive neural circuit hyperconnectivity in a fragile X syndrome model.BMC biology · 2020Article
- Article
- Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage.Biological psychiatry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss of the RNA-binding fragile X protein [fragile X mental retardation protein (FMRP)] results in a spectrum of cognitive deficits, the fragile X syndrome (FXS), while aging individuals with decreased protein levels present with a subset of these symptoms and tremor. The broad range of behavioral deficits likely reflects the ubiquitous distribution and multiple functions of the protein. FMRP loss is expected to affect multiple neuronal proteins and intracellular signaling pathways, whose identity and interactions are essential in understanding and ameliorating FXS symptoms. We used heterozygous mutants and targeted RNA interference-mediated abrogation in Drosophila to uncover molecular pathways affected by FMRP reduction. We present evidence that FMRP loss results in excess metabotropic glutamate receptor (mGluR) activity, attributable at least in part to elevation of the protein in affected neurons. Using high-resolution behavioral, genetic, and biochemical analyses, we present evidence that excess mGluR upon FMRP attenuation is linked to the cAMP decrement reported in patients and models, and underlies olfactory associative learning and memory deficits. Furthermore, our data indicate positive transcriptional regulation of the fly fmr1 gene by cAMP, via protein kinase A, likely through the transcription factor CREB. Because the human Fmr1 gene also contains CREB binding sites, the interaction of mGluR excess and cAMP signaling defects we present suggests novel combinatorial pharmaceutical approaches to symptom amelioration upon FMRP attenuation.
Indexed as
Identifiers
What OpenQuestion holds
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.