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Altered <i>glr-1</i> Expression after EtOH Withdrawal Is Linked to Associative Behavior Deficits in <i>C. elegans</i>.

Overview

Authors: Katie Brandel-Ankrapp1,2, Rachel N Arey2,3
ORCID iDs: Rachel N Arey
  1. Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030
  2. Center for Precision Environmental Health, Baylor College of Medicine, Houston, Texas 77030
  3. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030
Institutions: Baylor College of Medicine (United States)
Journal: eNeuro, volume 13, issue 7, pages ENEURO.0430-25.2026
Dates: received 19 November 2025; accepted 13 July 2026; published online 28 July 2026; in print July 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1523/eneuro.0430-25.2026 · PMID 42469032 · PMCID PMC13423511 · OpenAlex W7169612567
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: C. elegans (organism), cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Evoked potentials, fMRI & imaging
Keywords: AMPA receptors, C. elegans, CREB, ethanol, kinase, learning and memory
MeSH: Association Learning*, Caenorhabditis elegans Proteins*, Central Nervous System Depressants*, Ethanol*, Receptors, AMPA*, Substance Withdrawal Syndrome*, Animals, Animals, Genetically Modified, Caenorhabditis elegans, Cyclic AMP Response Element-Binding Protein, Memory, Signal Transduction (* major topic)
Topic: Genetics, Aging, and Longevity in Model Organisms (Aging, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: American Federation for Aging Research; Whitehall Foundation; HHS | NIH | NIH Office of the Director (DP2NS132372); NINDS NIH HHS (DP2 NS132372); NSF | National Science Foundation Graduate Research Fellowship Program (2023349937)
Citations: not cited yet (Europe PMC); 227 references in the paper

Abstract

Chronic ethanol (EtOH) exposure and withdrawal are linked to worsened memory and cognitive outcomes. One target of EtOH is the glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Both EtOH exposure and withdrawal influences AMPAR expression, function, and broad glutamate signaling. Previous work suggests that EtOH regulation of AMPARs drives behaviors related to dependence and memory phenotypes. However, due to the complexity of the mammalian brain, it is difficult to unravel the precise mechanism by which EtOH regulates AMPARs in mammals to modify specific memory behaviors. In Caenorhabditis elegans, GLR-1, an AMPAR ortholog, has tightly defined expression in relatively few neurons, conserved regulatory mechanisms, and is linked to molecularly conserved associative behaviors including those disrupted by EtOH. Using an established paradigm that exposes worms to chronic EtOH and cessation (“withdrawal”), we examined the relationship between EtOH withdrawal, associative memory, and GLR-1/AMPAR regulation. We found that withdrawal from chronic EtOH disrupts intermediate-term associative memory (ITM) in wild-type worms, phenocopying loss of GLR-1 function. ITM is rescued by EtOH reintroduction, suggesting a “withdrawal-like” phenotype. Losing GLR-1 occludes the ITM deficit and EtOH-ceased wild-type phenocopy glr-1 loss-of-function in other glr-1-regulated behaviors. Withdrawal broadly alters GLR-1 expression, downregulates glr-1, and increases CREB-mediated transcriptional activity in neurons in a JNK kinase-dependent manner. Loss of JNK and downstream transcription factor CREB prevent these EtOH withdrawal phenotypes. Overall, we have identified a transcriptional regulatory cascade driven by JNK–CREB signaling that may help neurons adapt glr-1 signaling in response to continuous EtOH exposure and abrupt withdrawal, leading to behavior deficits.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 2 authors, 6 keywords, 12 MeSH terms, 5 funders, 226 references.

Cite

This paper

Brandel-Ankrapp, K., & Arey, R. N. (2026). Altered <i>glr-1</i> Expression after EtOH Withdrawal Is Linked to Associative Behavior Deficits in <i>C. elegans</i>. eNeuro, 13(7), ENEURO.0430-25.2026. https://doi.org/10.1523/eneuro.0430-25.2026

BibTeX

@article{brandelankrapp2026altered,
author = {Brandel-Ankrapp, Katie and Arey, Rachel N},
title = {{Altered \<i\>glr-1\</i\> Expression after EtOH Withdrawal Is Linked to Associative Behavior Deficits in \<i\>C. elegans\</i\>}},
journal = {eNeuro},
year = {2026},
month = jul,
volume = {13},
number = {7},
pages = {ENEURO.0430--25.2026},
publisher = {Society for Neuroscience},
issn = {2373-2822},
doi = {10.1523/eneuro.0430-25.2026},
url = {https://doi.org/10.1523/eneuro.0430-25.2026},
pmid = {42469032},
pmcid = {PMC13423511}
}

RIS

TY - JOUR
AU - Brandel-Ankrapp, Katie
AU - Arey, Rachel N
TI - Altered <i>glr-1</i> Expression after EtOH Withdrawal Is Linked to Associative Behavior Deficits in <i>C. elegans</i>
T2 - eNeuro
J2 - eNeuro
PY - 2026
DA - 2026/07/30
VL - 13
IS - 7
SP - ENEURO.0430
EP - 25.2026
SN - 2373-2822
PB - Society for Neuroscience
DO - 10.1523/eneuro.0430-25.2026
UR - https://doi.org/10.1523/eneuro.0430-25.2026
LA - en
ER -

CSL-JSON

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