Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice

IntroductionEarly-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer’s disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence in...

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Main Authors: C. Leonardo Jimenez Chavez, Lauren E. Madory, Chris J. E. Denning, Edward C. Lee, Dylan T. Nguyen, Gavin P. Scheldrup, Karen K. Szumlinski
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Behavioral Neuroscience
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Online Access:https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1619889/full
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author C. Leonardo Jimenez Chavez
Lauren E. Madory
Chris J. E. Denning
Edward C. Lee
Dylan T. Nguyen
Gavin P. Scheldrup
Karen K. Szumlinski
Karen K. Szumlinski
Karen K. Szumlinski
author_facet C. Leonardo Jimenez Chavez
Lauren E. Madory
Chris J. E. Denning
Edward C. Lee
Dylan T. Nguyen
Gavin P. Scheldrup
Karen K. Szumlinski
Karen K. Szumlinski
Karen K. Szumlinski
author_sort C. Leonardo Jimenez Chavez
collection DOAJ
description IntroductionEarly-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer’s disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence induces what appears to be latent (>6 months post-drinking) changes in the expression of glutamate receptors and neuropathology markers within brain regions governing working and spatial memory, many of which precede the manifestation of overt cognitive anomalies.MethodsTo determine whether alcohol-induced changes in protein expression manifest within the hippocampus and prefrontal cortex at earlier times post-drinking, we conducted immunoblotting on tissue from mice with a subchronic history of binge-drinking (14 days of 2-h access to 10, 20 and 40% ethanol) during either adolescence or adulthood.ResultsWe previously reported that this binge-drinking regimen produces mild, age- and sex-selective, changes in working memory and spatial recall when behavior was assayed starting a 1 or 30 days withdrawal. Here, we provide evidence a subchronic binge-drinking history is sufficient to alter the expression of certain glutamate receptors and ADRD-related proteins during the first few months following drinking cessation. Further, these alcohol-induced protein changes are regionally specific and sex-selective.DiscussionThe present results add to our growing understanding of the long-term consequences of adolescent-onset binge-drinking of potential relevance to understanding individual variability in the cognitive consequences of heavy drinking.
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spelling doaj-art-72d7c23aabc84dc188b8df33db4654822025-08-20T03:12:26ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532025-07-011910.3389/fnbeh.2025.16198891619889Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J miceC. Leonardo Jimenez Chavez0Lauren E. Madory1Chris J. E. Denning2Edward C. Lee3Dylan T. Nguyen4Gavin P. Scheldrup5Karen K. Szumlinski6Karen K. Szumlinski7Karen K. Szumlinski8Department of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Psychological and Brain Sciences, University of California Santa Barbara, Santa Barbara, CA, United StatesDepartment of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, CA, United StatesNeuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA, United StatesIntroductionEarly-onset binge-drinking and biological sex are critical risk factors for the development of cognitive decline and neurodegeneration associated with Alzheimer’s disease and related dementias (ADRDs). Recently, we demonstrated that a prior history of binge-drinking during adolescence induces what appears to be latent (>6 months post-drinking) changes in the expression of glutamate receptors and neuropathology markers within brain regions governing working and spatial memory, many of which precede the manifestation of overt cognitive anomalies.MethodsTo determine whether alcohol-induced changes in protein expression manifest within the hippocampus and prefrontal cortex at earlier times post-drinking, we conducted immunoblotting on tissue from mice with a subchronic history of binge-drinking (14 days of 2-h access to 10, 20 and 40% ethanol) during either adolescence or adulthood.ResultsWe previously reported that this binge-drinking regimen produces mild, age- and sex-selective, changes in working memory and spatial recall when behavior was assayed starting a 1 or 30 days withdrawal. Here, we provide evidence a subchronic binge-drinking history is sufficient to alter the expression of certain glutamate receptors and ADRD-related proteins during the first few months following drinking cessation. Further, these alcohol-induced protein changes are regionally specific and sex-selective.DiscussionThe present results add to our growing understanding of the long-term consequences of adolescent-onset binge-drinking of potential relevance to understanding individual variability in the cognitive consequences of heavy drinking.https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1619889/fulladolescencegroup 1 metabotropic glutamate receptorstauprefrontal cortexhippocampussex differences
spellingShingle C. Leonardo Jimenez Chavez
Lauren E. Madory
Chris J. E. Denning
Edward C. Lee
Dylan T. Nguyen
Gavin P. Scheldrup
Karen K. Szumlinski
Karen K. Szumlinski
Karen K. Szumlinski
Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
Frontiers in Behavioral Neuroscience
adolescence
group 1 metabotropic glutamate receptors
tau
prefrontal cortex
hippocampus
sex differences
title Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
title_full Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
title_fullStr Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
title_full_unstemmed Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
title_short Examination of age- and sex-related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge-drinking in C57BL/6J mice
title_sort examination of age and sex related changes in protein expression within the hippocampus and prefrontal cortex during withdrawal from a subchronic history of binge drinking in c57bl 6j mice
topic adolescence
group 1 metabotropic glutamate receptors
tau
prefrontal cortex
hippocampus
sex differences
url https://www.frontiersin.org/articles/10.3389/fnbeh.2025.1619889/full
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