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<p>Chronic alcohol drinking increases susceptibility to cognitive impairment; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of chronic alcohol drinking on working and recognition memory in a Marchigian Sardinian alcohol-preferring (msP) rat line. Due to interest in insulin-based medications for alcohol use disorder, we examined insulin/insulin-like growth factor 1 (IGF-1) genes in the prelimbic (PL) and infralimbic (IL) medial prefrontal cortex, a region linked to alcohol dependence and cognition. Male and female msPs received access to alcohol (20% <i>v/v</i>) and water (H<sub>2</sub>O) using a group-housed 2 bottle-choice drinking paradigm for several weeks, while controls received H<sub>2</sub>O only. After five weeks, the radial arm maze and novel object recognition tasks evaluated working and recognition memory. At the end of the study, genes encoding for insulin/IGF-1, their receptors, and downstream effectors were assessed in the PL, IL and hippocampus CA1 (CA1), three main regions involved in working and recognition memory processing. Genes regulating brain plasticity were also assessed. Females consumed more alcohol than males. Chronic alcohol exposure selectively impaired recognition memory in males, while working memory remained unaffected in both sexes. Chronic alcohol exposure altered transcription of insulin/IGF-1 signaling components. In females, chronic alcohol reduced <i>Ins</i> transcript levels in the IL, while increasing <i>Insr</i> expression in the PL, but not in the CA1. In males, chronic alcohol reduced <i>Igf1r</i> transcript levels in the IL, but not PL or CA1. Across both sexes and all regions, chronic alcohol decreased <i>Irs2</i>, a downstream effector of insulin/IGF-1, transcript levels. Lastly, we observed some alterations in genes linked to memory and plasticity including <i>Bdnf</i>, <i>TrkB</i>, <i>Psd95</i>, and <i>Pkmζ</i>. Together, these findings suggest that chronic alcohol drinking impairs recognition memory in males, while broadly disrupting metabolic and plasticity-associated genes in the mPFC and CA1.</p>

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Chronic Alcohol Drinking Impairs Recognition Memory And Insulin-Associated Genes In The Medial Prefrontal Cortex

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月16日

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  • Bryan Cruz,
  • Michela Palmisano,
  • Alex Hiroto,
  • Ryan Bullard,
  • Ismael Muñoz Gil,
  • Alexia Anjos-Santos,
  • Angela E. Gonzalez,
  • Celsey M. St. Onge,
  • Valentina Vozella,
  • Roberto Ciccocioppo,
  • Marisa Roberto

摘要

Chronic alcohol drinking increases susceptibility to cognitive impairment; however, the underlying mechanisms remain unclear. In this study, we investigated the effects of chronic alcohol drinking on working and recognition memory in a Marchigian Sardinian alcohol-preferring (msP) rat line. Due to interest in insulin-based medications for alcohol use disorder, we examined insulin/insulin-like growth factor 1 (IGF-1) genes in the prelimbic (PL) and infralimbic (IL) medial prefrontal cortex, a region linked to alcohol dependence and cognition. Male and female msPs received access to alcohol (20% v/v) and water (H2O) using a group-housed 2 bottle-choice drinking paradigm for several weeks, while controls received H2O only. After five weeks, the radial arm maze and novel object recognition tasks evaluated working and recognition memory. At the end of the study, genes encoding for insulin/IGF-1, their receptors, and downstream effectors were assessed in the PL, IL and hippocampus CA1 (CA1), three main regions involved in working and recognition memory processing. Genes regulating brain plasticity were also assessed. Females consumed more alcohol than males. Chronic alcohol exposure selectively impaired recognition memory in males, while working memory remained unaffected in both sexes. Chronic alcohol exposure altered transcription of insulin/IGF-1 signaling components. In females, chronic alcohol reduced Ins transcript levels in the IL, while increasing Insr expression in the PL, but not in the CA1. In males, chronic alcohol reduced Igf1r transcript levels in the IL, but not PL or CA1. Across both sexes and all regions, chronic alcohol decreased Irs2, a downstream effector of insulin/IGF-1, transcript levels. Lastly, we observed some alterations in genes linked to memory and plasticity including Bdnf, TrkB, Psd95, and Pkmζ. Together, these findings suggest that chronic alcohol drinking impairs recognition memory in males, while broadly disrupting metabolic and plasticity-associated genes in the mPFC and CA1.