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Cited by 99Prenatal Substance Exposure EffectsAlcohol Consumption and Health EffectsFetal and Pediatric Neurological Disorders

Alcohol Exposure Decreases CREB Binding Protein Expression and Histone Acetylation in the Developing Cerebellum

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Guo, Weixiang, Crossey, Erin L., Zhang, Li, Zucca, Stefano, George, Olivia L., Valenzuela, C. Fernando, Zhao, Xinyu·2011·PLoS ONE
DOI 10.1371/journal.pone.0019351PMC PMC3104983
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Abstract

BACKGROUND: Fetal alcohol exposure affects 1 in 100 children making it the leading cause of mental retardation in the US. It has long been known that alcohol affects cerebellum development and function. However, the underlying molecular mechanism is unclear. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrate that CREB binding protein (CBP) is widely expressed in granule and Purkinje neurons of the developing cerebellar cortex of naïve rats. We also show that exposure to ethanol during the 3(rd) trimester-equivalent of human pregnancy reduces CBP levels. CBP is a histone acetyltransferase, a component of the epigenetic mechanism controlling neuronal gene expression. We further demonstrate that the acetylation of both histone H3 and H4 is reduced in the cerebellum of ethanol-treated rats. CONCLUSIONS/SIGNIFICANCE: These findings indicate that ethanol exposure decreases the expression and function of CBP in the developing cerebellum. This effect of ethanol may be responsible for the motor coordination deficits that characterize fetal alcohol spectrum disorders.

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  • This mechanism observed with the use of amphetamines leads to neurodegeneration and lower cell survival.

    “This mechanism observed with the use of amphetamines leads to neurodegeneration and lower cell survival [216].”

    From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [216]

    The Results and Discussion address ethanol exposure in the developing cerebellum, not amphetamine use. The Discussion mentions apoptosis after high-dose ethanol exposure but does not establish that the proposed CBP mechanism causes neurodegeneration or reduced cell survival. Searches for amphetamines and for the claimed survival outcome found no passage addressing the claim. (LLM, conf=0.76)

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Cited by

Sorted by citations

Authors
Guo, W., Crossey, E. L., Zhang, L., Zucca, S., George, O. L., Valenzuela, C. F., & Zhao, X.
Affiliations
University of New Mexico (US)
Corresponding author
  • Valenzuela, C. Fernando
  • Zhao, Xinyu
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2011-05-31
Volume
6
Issue
5
Pages
e19351
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0019351
PMC
PMC3104983
OpenAlex
W2076731913
Cited by
99
References
2
Citations by year
2024: 2 · 2023: 5 · 2022: 4 · 2021: 7 · 2020: 10 · 2019: 5 · 2018: 6 · 2017: 19 · 2016: 5 · 2015: 7 · 2014: 13 · 2013: 10 · 2012: 6
FWCI
8.59
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Institutes of Health (MH080434, AA017068)
  • National Institute on Alcohol Abuse and Alcoholism (R37AA015614, AA-14973, AA15614, P20AA017068, R01AA014973, R56AA014973, R01AA015614)
  • National Institute of Mental Health (R01MH078972, MH078972, MH080434, R01MH080434)
  • National Institute of General Medical Sciences (K12GM088021)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
Keywords
prenatal alcohol exposure, ethanol, CREB-binding protein, histone acetylation, histone H3, histone H4, cerebellar development, Purkinje cells, granule neurons, epigenetic regulation, fetal alcohol spectrum disorders, motor coordination deficits, third trimester
MeSH terms
Acetylation, Ethanol, Animals, Animals, Newborn, Cerebellum, Female, Histones, Male, Pregnancy, Blotting, Western, Gene Expression Regulation, Developmental, CREB-Binding Protein, Rats

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