Evidence map›Paper›PMID 38785269›Full record

ArticleDisease models & mechanisms2024

A small-molecule TrkB ligand improves dendritic spine phenotypes and atypical behaviors in female Rett syndrome mice.

Destynie Medeiros, Karen Ayala-Baylon, Hailey Egido-Betancourt, Eric Miller, Christopher Chapleau, Holly Robinson, Mary L Phillips, Tao Yang, Frank M Longo, Wei Li and 1 more

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Article in Disease models & mechanisms, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

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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

6 citing papers in PubMed.

  1. Article
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  4. Review
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  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Destynie MedeirosDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Karen Ayala-BaylonDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hailey Egido-BetancourtDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Eric MillerDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Christopher ChapleauDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Holly RobinsonDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Mary L PhillipsDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Tao YangDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Frank M LongoDepartment of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Wei LiDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Lucas Pozzo-MillerDepartment of Neurobiology, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.ORCID 0000-0001-6085-5527

Funding

UAB Research Training Program in Neurobiology of Cognition and Cognitive DisordersT32NS061788 · NINDS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Farah Dominique Lubin · 2008 to 2026
$4.5M
Role of the Hippocampal-mPFC Pathway in Social Memory Deficits in AutismR01MH118563 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI POZZO-MILLER, LUCAS D · 2019 to 2022
$1.6M
Reversing BDNF Impairments in Rett Mice with TRPC Channel ActivatorsR21HD074418 · NICHD · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI POZZO-MILLER, LUCAS D · 2013 to 2014
$399k
National Institute of Child Health and Human Development HD-074418NICHD NIH HHS R21 HD074418NIH HHSNIMH NIH HHS MH-118563-01NIMH NIH HHS R01 MH118563NINDS NIH HHS T32 NS061788NINDS NIH HHS T32-NS061788Rett Syndrome Research Trust
6 · The paper itself

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in MECP2, which encodes methyl-CpG-binding protein 2, a transcriptional regulator of many genes, including brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improve atypical phenotypes in Mecp2 mutant mice. Due to the low blood-brain barrier permeability of BDNF itself, we tested the effects of LM22A-4, a brain-penetrant, small-molecule ligand of the BDNF receptor TrkB (encoded by Ntrk2), on dendritic spine density and form in hippocampal pyramidal neurons and on behavioral phenotypes in female Mecp2 heterozygous (HET) mice. A 4-week systemic treatment of Mecp2 HET mice with LM22A-4 restored spine volume in MeCP2-expressing neurons to wild-type (WT) levels, whereas spine volume in MeCP2-lacking neurons remained comparable to that in neurons from female WT mice. Female Mecp2 HET mice engaged in aggressive behaviors more than WT mice, the levels of which were reduced to WT levels by the 4-week LM22A-4 treatment. These data provide additional support to the potential usefulness of novel therapies not only for RTT but also to other BDNF-related disorders.

Indexed as

Behavior, AnimalBenzamidesDendritic SpinesMethyl-CpG-Binding Protein 2PhenotypeReceptor, trkBRett SyndromeAnimalsBrain-Derived Neurotrophic FactorDisease Models, AnimalFemaleHeterozygoteHippocampusLigandsMiceMice, Inbred C57BLBenzamidesBrain-Derived Neurotrophic FactorLigandsMecp2 protein, mouseMethyl-CpG-Binding Protein 2N,N',N'-tris(2-hydroxyethyl)-1,3,5-benzenetricarboxamideReceptor, trkBBDNFHippocampusLM22A-4MeCP2Pyramidal neuron

Identifiers

PMID38785269
PMCPMC11139040

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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.