Evidence map›Paper›PMID 39607825›Full record

ArticleCell reports2024

Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders.

Josep Carbonell-Roig, Alina Aaltonen, Karin Wilson, Maya Molinari, Veronica Cartocci, Avery McGuirt, Eugene Mosharov, Jan Kehr, Ori J Lieberman, David Sulzer and 2 more

Abstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors.

Josep Carbonell-RoigDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Alina AaltonenDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Karin WilsonDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Maya MolinariDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Veronica CartocciDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden.
Avery McGuirtDepartment of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
Eugene MosharovDepartment of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
Jan KehrPronexus Analytical AB, 16733 Stockholm-Bromma, Sweden.
Ori J LiebermanDepartment of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA; Department of Neurology, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.
David SulzerDepartment of Psychiatry, Columbia University Irving Medical Center, New York, NY 10032, USA; New York State Psychiatric Institute, New York, NY 10032, USA.
Anders BorgkvistDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden. Electronic address: anders.borgkvist@ki.se.
Emanuela SantiniDepartment of Neuroscience, Karolinska Institute, 17177 Stockholm, Sweden. Electronic address: emanuela.santini@ki.se.

Funding

The Dopamine Synapse and Associative LearningR01DA007418 · NIDA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI David Sulzer · 1999 to 2026
$9.4M
Regulation of striatal maturation by dopamine and macroautophagy: implications for neuropsychiatric disordersF30MH114390 · NIMH · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI LIEBERMAN, ORI J · 2017 to 2020
$181k
NIDA NIH HHS R01 DA007418NIMH NIH HHS F30 MH114390
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) consists of diverse neurodevelopmental conditions where core behavioral symptoms are critical for diagnosis. Altered dopamine (DA) neurotransmission in the striatum has been suggested to contribute to the behavioral features of ASD. Here, we examine DA neurotransmission in a mouse model of ASD characterized by elevated expression of eukaryotic initiation factor 4E (eIF4E), a key regulator of cap-dependent translation, using a comprehensive approach that encompasses genetics, behavior, synaptic physiology, and imaging. The results indicate that increased eIF4E expression leads to behavioral inflexibility and impaired striatal DA release. The loss of normal DA neurotransmission is due to a defect in nicotinic receptor signaling that regulates calcium dynamics in dopaminergic axons. These findings provide a mechanistic understanding of ASD symptoms and offer a foundation for targeted therapeutic interventions by revealing the intricate interplay between eIF4E, DA neurotransmission, and behavioral flexibility.

Indexed as

AcetylcholineAutism Spectrum DisorderDisease Models, AnimalDopamineEukaryotic Initiation Factor-4ESynaptic TransmissionAnimalsMaleMiceMice, Inbred C57BLMice, TransgenicReceptors, NicotinicAcetylcholineDopamineeIF4E protein, mouseEukaryotic Initiation Factor-4EReceptors, Nicotinicautism spectrum disorderbehavioral inflexibilityCP: NeurosciencedopamineeIF4Efast-scan cyclic voltammetrymouse modelsnicotinic acetylcholine receptorsprotein synthesisstriatum

Identifiers

PMID39607825
PMCPMC12775367

What Socratic holds

Textmetadata
LicenceCC BY
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.