Evidence map›Paper›PMID 42155452›Full record

ArticleNeuron2026

Translatome profiling reveals opposing alterations in inhibitory and excitatory neurons of fragile X mice and identifies EPAC2 as a therapeutic target.

Anand Suresh, Nazim Kourdougli, Toshihiro Nomura, Jessie E Buth, Soledad Miranda-Rottmann, Carlos A Sánchez-León, Michelle W Wu, Sofia M Nelson, Lauren T Wall, Anne T Tran and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Anand SureshDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Nazim KourdougliDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Toshihiro NomuraDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Jessie E ButhNeuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Soledad Miranda-RottmannDepartment of Neurosciences, Faculty of Medicine, University of Montréal, Montréal, QC H3T 1C5, Canada; CHU Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada.
Carlos A Sánchez-LeónDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Michelle W WuDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA; Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA 90095, USA; UCLA-Caltech Medical Scientist Training Program, Los Angeles, CA, USA.
Sofia M NelsonDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Lauren T WallDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Anne T TranDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA.
Roberto ArayaDepartment of Neurosciences, Faculty of Medicine, University of Montréal, Montréal, QC H3T 1C5, Canada; CHU Sainte-Justine Research Center, Montréal, QC H3T 1C5, Canada.
Anis ContractorDepartment of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Michael J GandalDepartments of Psychiatry and Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; The Lifespan Brain Institute, Penn Med and the Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Carlos Portera-CailliauDepartment of Neurology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Neurobiology, David Geffen School of Medicine at the University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: cpcailliau@mednet.ucla.edu.

Funding

UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA IDDRC: Translational CoreP50HD103557 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Michael Gandal · 2020 to 2026
$9.6M
Imaging the origin of dendritic spine abnormalities in fragile X miceR01HD054453 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Carlos Portera-Cailliau · 2007 to 2026
$6.5M
Isoform-level probabilistic transcriptome-wide association to undercover neurogenetic mechanisms underlying complex psychiatric traitsR01MH121521 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.4M
Cortical Interneuron Dysfunction in Fragile X SyndromeR01HD108370 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Anis Contractor, Carlos Portera-Cailliau · 2022 to 2026
$2.5M
Circuit Disruptions Underlying Atypical Sensory Processing in Fragile X SyndromeR01NS117597 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ERICKSON, CRAIG, PORTERA-CAILLIAU, CARLOS · 2020 to 2024
$2.3M
Cellular and developmental genetic regulation of 3' isoform diversity in the human brain and its contribution to neuropsychiatric disordersR01MH137578 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI Michael Gandal, Ophir Shalem · 2024 to 2026
$2.1M
Effectors of presynaptic cAMP dependent potentiation at mossy fiber synapses_Diversity SupplementR01MH130428 · NIMH · NORTHWESTERN UNIVERSITY AT CHICAGO · PI CONTRACTOR, ANIS, SAVAS, JEFFREY NICHOLAS · 2022 to 2024
$2.1M
Role of Intracortical Mechanisms Vs. Bottom-Up Influences in Developmental Desynchronization of Cortical Network ActivityF30HD117619 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Michelle W. Wu · 2025 to 2026
$92k
NICHD NIH HHS F30 HD117619NICHD NIH HHS P50 HD103557NICHD NIH HHS R01 HD054453NICHD NIH HHS R01 HD108370NIGMS NIH HHS T32 GM008042NIMH NIH HHS R01 MH121521NIMH NIH HHS R01 MH130428NIMH NIH HHS R01 MH137578NINDS NIH HHS R01 NS117597
6 · The paper itself

Abstract

Symptoms of fragile X syndrome (FXS), the leading monogenic cause of intellectual disability and autism, are thought to arise from an excitation/inhibition (E/I) imbalance. Here, we leverage cell-type-specific mRNA sequencing to profile molecular alterations in cortical excitatory (Camk2) and inhibitory (Pvalb) neurons in Fmr1 knockout (KO) mice, integrating transcriptomic results with circuit and behavioral readouts to prioritize novel therapeutic targets. We uncovered significant genotype-by-cell type interactions for differential gene expression in Camk2a and Pvalb translatomes, and, strikingly, the underlying signaling pathways were often altered in opposite directions. Among the 184 differentially expressed genes that were concordantly dysregulated across both cell types, only Rapgef4 (a.k.a., exchange protein direftly activated by cAMP 2 [Epac2]; upregulated in Fmr1 KO) was also a fragile X messenger ribonucleoprotein (FMRP) target, brain-enriched, and associated with neurodevelopmental disorders. Treatment of Fmr1 KO mice with a specific EPAC2 antagonist restored cortical circuit function and ameliorated multiple behavioral phenotypes. Thus, EPAC2 should be considered a potential therapeutic target for FXS.

Indexed as

Fragile X SyndromeGuanine Nucleotide Exchange FactorsNeuronsAnimalsCalcium-Calmodulin-Dependent Protein Kinase Type 2Cerebral CortexFragile X Messenger Ribonucleoprotein 1MaleMiceMice, KnockoutTranscriptomeCalcium-Calmodulin-Dependent Protein Kinase Type 2Camk2a protein, mouseFmr1 protein, mouseFragile X Messenger Ribonucleoprotein 1Guanine Nucleotide Exchange FactorsRapgef4 protein, mouseautism spectrum disordercalcium imagingclinical and translational medicineFmr1 knockoutmolecular and cellular neuroscienceneurodevelopmental disorder, parvalbuminRapgef4RiboTagRNA sequencingtactile defensivenesstranscriptomics

Identifiers

PMID42155452
PMCPMC13242833

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 Socratic graph.