Evidence map›Paper›PMID 38734844›Full record

ArticleMolecular psychiatry2024

Reduction of APOE accounts for neurobehavioral deficits in fetal alcohol spectrum disorders.

Hye M Hwang, Satoshi Yamashita, Yu Matsumoto, Mariko Ito, Alex Edwards, Junko Sasaki, Dipankar J Dutta, Shahid Mohammad, Chiho Yamashita, Leah Wetherill and 9 more

Abstract read
In one paragraph

Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

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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

19 authors.

Hye M Hwang *Center for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Satoshi Yamashita *Center for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.ORCID 0000-0003-2294-8225
Yu MatsumotoCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Mariko ItoCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Alex EdwardsCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Junko SasakiCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.ORCID 0009-0008-9703-3509
Dipankar J DuttaCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Shahid MohammadCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Chiho YamashitaCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA.
Leah WetherillDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0003-2888-9051
Tae-Hwi Schwantes-AnDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0001-6387-0095
Marco AbreuDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
Amanda H MahnkeDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University School of Medicine, Bryan, TX, USA.
Sarah N MattsonCenter for Behavioral Teratology, San Diego State University, San Diego, CA, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.ORCID 0000-0002-5549-2212
Rajesh C MirandaDepartment of Neuroscience and Experimental Therapeutics, Texas A&M University School of Medicine, Bryan, TX, USA.
Christina ChambersDepartment of Pediatrics, University of California San Diego, San Diego, CA, USA.
Masaaki ToriiCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA. mtorii@childrensnational.org.ORCID 0000-0003-0162-7924
Kazue Hashimoto-ToriiCenter for Neuroscience Research, The Children's Research Institute, Children's National Hospital, Washington, DC, USA. khtorii@childrensnational.org.ORCID 0000-0003-4001-8259

Funding

FASD in San Diego and Moscow (U01 Research Project)U01AA014834 · NIAAA · SAN DIEGO STATE UNIVERSITY · PI SARAH N MATTSON WELLER · 2003 to 2026
$12.4M
Whole Body Effects of PAE Across the Life Span: Early Markers of & Clinical Interventions for Children and Adolescents in UkraineU01AA014835 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHRISTINA CHAMBERS · 2003 to 2026
$12.1M
Neurobehavioral Evaluation CoreP50HD105328 · NICHD · CHILDREN'S RESEARCH INSTITUTE · PI WILLIAM Davis GAILLARD · 2021 to 2026
$9.3M
Image Analysis of Neurofacial Effects of Prenatal AlcoholExposureU01AA014809 · NIAAA · UNIVERSITY OF OXFORD · PI Michael Suttie · 2007 to 2026
$5.8M
Dissecting the genetic contributions to fetal alcohol spectrum disordersU01AA026103 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI FOROUD, TATIANA M. · 2017 to 2021
$2.6M
Mechanisms and treatments of learning deficits in Fetal Alcohol Spectrum DisordersR01AA026272 · NIAAA · CHILDREN'S RESEARCH INSTITUTE · PI HASHIMOTO-TORII, KAZUE, TORII, MASAAKI · 2019 to 2023
$2.4M
The roles of alcohol-inducible RNA-operons in the fetal brainR01AA025215 · NIAAA · CHILDREN'S RESEARCH INSTITUTE · PI HASHIMOTO-TORII, KAZUE · 2016 to 2020
$2.0M
Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) Data Coordination ResourceU24AA030169 · NIAAA · INDIANA UNIVERSITY INDIANAPOLIS · PI Leah Wetherill · 2022 to 2026
$1.0M
Roles of Very Long Chain Fatty Acids in Neurobehavior Deficits in FASDF31AA027693 · NIAAA · CHILDREN'S RESEARCH INSTITUTE · PI HWANG, HYE · 2019 to 2021
$133k
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) F31AA027693Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) P50HD105328Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01AA025215Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01AA026272Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U01AA014809Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U01AA014834Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U01AA014835Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U01AA025103Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) U24AA030169NIAAA NIH HHS F31 AA027693NIAAA NIH HHS R01 AA025215NIAAA NIH HHS R01 AA026272NIAAA NIH HHS U01 AA014809NIAAA NIH HHS U01 AA014834NIAAA NIH HHS U01 AA014835NIAAA NIH HHS U01 AA026103NIAAA NIH HHS U24 AA030169NICHD NIH HHS P50 HD105328
6 · The paper itself

Abstract

A hallmark of fetal alcohol spectrum disorders (FASD) is neurobehavioral deficits that still do not have effective treatment. Here, we present that reduction of Apolipoprotein E (APOE) is critically involved in neurobehavioral deficits in FASD. We show that prenatal alcohol exposure (PAE) changes chromatin accessibility of Apoe locus, and causes reduction of APOE levels in both the brain and peripheral blood in postnatal mice. Of note, postnatal administration of an APOE receptor agonist (APOE-RA) mitigates motor learning deficits and anxiety in those mice. Several molecular and electrophysiological properties essential for learning, which are altered by PAE, are restored by APOE-RA. Our human genome-wide association study further reveals that the interaction of PAE and a single nucleotide polymorphism in the APOE enhancer which chromatin is closed by PAE in mice is associated with lower scores in the delayed matching-to-sample task in children. APOE in the plasma is also reduced in PAE children, and the reduced level is associated with their lower cognitive performance. These findings suggest that controlling the APOE level can serve as an effective treatment for neurobehavioral deficits in FASD.

Indexed as

Apolipoproteins EBrainFetal Alcohol Spectrum DisordersGenome-Wide Association StudyPrenatal Exposure Delayed EffectsAnimalsChildDisease Models, AnimalEthanolFemaleHumansMaleMiceMice, Inbred C57BLPolymorphism, Single NucleotidePregnancyApolipoproteins EEthanol

Identifiers

PMID38734844
PMCPMC11541007

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Registered trials

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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.