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Cited by 31Neuroscience and Neuropharmacology ResearchPrenatal Substance Exposure EffectsAnesthesia and Neurotoxicity Research

Changes in the Adult GluN2B Associated Proteome following Adolescent Intermittent Ethanol Exposure

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Swartzwelder, H. Scott, Risher, Mary-Louise, Miller, Kelsey M., Colbran, Roger J., Winder, Danny G., Wills, Tiffany A.·2016·PLOS ONE
DOI 10.1371/journal.pone.0155951PMC PMC4877005
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Abstract

Adolescent alcohol use is the strongest predictor for alcohol use disorders. In rodents, adolescents have distinct responses to acute ethanol, and prolonged alcohol exposure during adolescence can maintain these phenotypes into adulthood. One brain region that is particularly sensitive to the effects of both acute and chronic ethanol exposure is the hippocampus. Adolescent intermittent ethanol exposure (AIE) produces long lasting changes in hippocampal synaptic plasticity and dendritic morphology, as well as in the susceptibility to acute ethanol-induced spatial memory impairment. Given the pattern of changes in hippocampal structure and function, one potential target for these effects is the ethanol sensitive GluN2B subunit of the NMDA receptor, which is known to be involved in synaptic plasticity and dendritic morphology. Thus we sought to determine if there were persistent changes in hippocampal GluN2B signaling cascades following AIE. We employed a previously validated GluN2B-targeted proteomic strategy that was used to identify novel signaling mechanisms altered by chronic ethanol exposure in the adult hippocampus. We collected adult hippocampal tissue (P70) from rats that had been given 2 weeks of AIE from P30-45. Tissue extracts were fractionated into synaptic and non-synaptic pools, immuno-precipitated for GluN2B, and then analyzed using proteomic methods. We detected a large number of proteins associated with GluN2B. AIE produced significant changes in the association of many proteins with GluN2B in both synaptic and non-synaptic fractions. Intriguingly the number of proteins changed in the non-synaptic fraction was double that found in the synaptic fraction. Some of these proteins include those involved in glutamate signaling cytoskeleton rearrangement, calcium signaling, and plasticity. Disruptions in these pathways may contribute to the persistent cellular and behavioral changes found in the adult hippocampus following AIE. Further, the robust change in non-synaptic proteins suggests that AIE may prime this signaling pathway for future ethanol exposures in adulthood.

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  • Evidence suggests adolescent alcohol exposure alters glutamatergic function, and increases in hippocampal glutamate have been linked to schizophrenia and psychosis.

    “This finding is particularly relevant given the evidence suggesting AAE alters glutamatergic function [73, 74], and increases in hippocampal glutamate have been linked to schizophrenia [75] and psychosis [76].”

    From Consequences of adolescent drug use (2023) · cites this paper as [73]

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Cited by

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  • Consequences of adolescent drug use

    Steinfeld, M. R., & Torregrossa, M. M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02590-4 · Cited by 237 · see citing works

    “This fi nding is particularly relevant given the evidence suggesting AAE alters glutamatergic function [73, 74], and increases in hippocampal glutamate have been linked to schizophrenia [75] and psychosis [76].”
    Background

Authors
Swartzwelder, H. S., Risher, M.-L., Miller, K. M., Colbran, R. J., Winder, D. G., & Wills, T. A.
Affiliations
  • Duke Medical Center (US)
  • Vanderbilt University (US)
  • Louisiana State University (US)
Corresponding author
Wills, Tiffany A.
ORCID
Venue
PLOS ONE
Publisher
Public Library of Science (PLoS)
Published
2016-05-23
Volume
11
Issue
5
Pages
e0155951
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0155951
PMC
PMC4877005
OpenAlex
W2395734408
Cited by
31
References
7
Citations by year
2026: 2 · 2025: 1 · 2024: 1 · 2023: 6 · 2022: 1 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 1 · 2017: 2
FWCI
1.88
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • U.S. Department of Veterans Affairs (1IK2BX002505)
  • National Institute on Alcohol Abuse and Alcoholism (2U01AA019925, K99-AA22651, R01-AA019455)
  • National Institute of Mental Health (R01-MH063232)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
Keywords
GluN2B, NMDA receptor, adolescent intermittent ethanol exposure, hippocampus, adult hippocampus, synaptic proteome, synaptic plasticity, dendritic morphology, glutamate signaling, calcium signaling, cytoskeleton rearrangement, alcoholism, ethanol-induced memory impairment
MeSH terms
Underage Drinking, Adolescent, Ethanol, Animals, Disease Models, Animal, Female, Hippocampus, Humans, Male, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Proteome, Proteomics, Protein Interaction Maps

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