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Proteomic Profile of a Chronic Binge Ethanol Exposure Model
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    Proteomic Profile of a Chronic Binge Ethanol Exposure Model
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    • Phillip Starski
      Phillip Starski
      Neuroscience Program, Mayo Clinic, Rochester, Minnesota 55905, United States
    • Lee Peyton
      Lee Peyton
      Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, Minnesota 55905, United States
      More by Lee Peyton
    • Alfredo Oliveros
      Alfredo Oliveros
      Department of Neurologic Surgery, Mayo Clinic, Rochester, Minnesota 55905, United States
    • Carrie J. Heppelmann
      Carrie J. Heppelmann
      Proteomics Research Center, Mayo Clinic, Rochester, Minnesota 55905, United States
    • Surendra Dasari
      Surendra Dasari
      Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota 55905, United States
    • Doo-Sup Choi*
      Doo-Sup Choi
      Neuroscience Program,  Department of Molecular Pharmacology and Experimental Therapeutics  and  Department of Psychiatry and Psychology, Mayo Clinic, Rochester, Minnesota 55905, United States
      *Tel: 507-284-5602. Fax: 507-284-1762. E-mail: [email protected]
      More by Doo-Sup Choi
    Other Access OptionsSupporting Information (1)

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2019, 18, 9, 3492–3502
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    https://doi.org/10.1021/acs.jproteome.9b00394
    Published July 22, 2019
    Copyright © 2019 American Chemical Society

    Abstract

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    Chronic binge alcohol drinking is known to increase risky decision through pathological impulsive behaviors. Recently, we established a novel rodent model of ethanol-induced waiting impulsivity using 5-choice serial reaction time task (5-CSRTT) in mice. However, molecular mechanisms underlying the chronic binge ethanol-induced waiting impulsivity is not well characterized. Among brain regions involved in impulsivity, the anterior cingulate cortex (ACC) is a major neural substrate for mediating the 5-CSRTT-based waiting impulsivity. Thus, we sought to determine the ACC proteomic profile using label-free proteomics of mice exhibiting ethanol-induced impulsivity. Ingenuity pathway analysis revealed that impulsivity-related proteins involved in ion channel complexes such as KCNIP3 (potassium voltage-gated channel interacting protein 3) and CACNG2 (calcium voltage-gated channel auxiliary subunit gamma 2) are downregulated in the ACC. We identified significant protein expression changes in the mechanistic target of rapamycin (mTOR) canonical pathway between control and ethanol-induced impulsive mice. Impulsive mice showed over 60% of proteins involved in the mTOR canonical pathway have been altered. This pathway has been previously implicated in the neuroadaptation in drugs of abuse and impulsivity. We found substantial changes in the protein levels involved in neurological disorders such as schizophrenia and Alzheimer’s disease. Our findings provide a neuroproteomic profile of ethanol-induced impulsive mice.

    Copyright © 2019 American Chemical Society

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    Supporting Information

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jproteome.9b00394.

    • Behavioral data of the entire cohort; behavioral data of the mice used for proteomic analysis; mass spectrometry quality control; top upregulated proteins; top downregulated proteins (PDF)

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    This article is cited by 8 publications.

    1. Ada Man-Choi Ho, Mina P. Peyton, Samantha J. Scaletty, Sarah Trapp, Areonna Schreiber, Benjamin J. Madden, Doo-Sup Choi, Douglas B. Matthews. Chronic Intermittent Ethanol Exposure Alters Behavioral Flexibility in Aged Rats Compared to Adult Rats and Modifies Protein and Protein Pathways Related to Alzheimer’s Disease. ACS Omega 2022, 7 (50) , 46260-46276. https://doi.org/10.1021/acsomega.2c04528
    2. Phillip Starski, Addyson Siegle, F. Woodward Hopf. Engagement for alcohol escalates in the 5-choice serial reaction time task after intermittent access. Alcohol 2024, 115 , 79-92. https://doi.org/10.1016/j.alcohol.2024.01.004
    3. Yingping Ma, Shaofei Jiang, Xin Zhao, Shen Li, Liping Chen, Zhe Zhao, Wei Shen, Yan Wu, Haitao Wu. CaMKIIα neurons in the anterior insular cortex regulate attention behavior in mice. Frontiers in Neural Circuits 2023, 17 https://doi.org/10.3389/fncir.2023.1197541
    4. Phillip Starski, Danielle Maulucci, Hunter Mead, Frederic Hopf. Adaptation of the 5-choice serial reaction time task to measure engagement and motivation for alcohol in mice. Frontiers in Behavioral Neuroscience 2022, 16 https://doi.org/10.3389/fnbeh.2022.968359
    5. Marcos Ucha, David Roura-Martínez, Emilio Ambrosio, Alejandro Higuera-Matas. The role of the mTOR pathway in models of drug-induced reward and the behavioural constituents of addiction. Journal of Psychopharmacology 2020, 34 (11) , 1176-1199. https://doi.org/10.1177/0269881120944159
    6. Pei Shang, Daniel Lindberg, Phillip Starski, Lee Peyton, Sa-Ik Hong, Sun Choi, Doo-Sup Choi. Chronic Alcohol Exposure Induces Aberrant Mitochondrial Morphology and Inhibits Respiratory Capacity in the Medial Prefrontal Cortex of Mice. Frontiers in Neuroscience 2020, 14 https://doi.org/10.3389/fnins.2020.561173
    7. Yan Zhou, Yupu Liang, Mary Jeanne Kreek. mTORC1 pathway is involved in the kappa opioid receptor activation-induced increase in excessive alcohol drinking in mice. Pharmacology Biochemistry and Behavior 2020, 195 , 172954. https://doi.org/10.1016/j.pbb.2020.172954
    8. Reginald Cannady, Sudarat Nimitvilai-Roberts, Sarah D. Jennings, John J. Woodward, Patrick J. Mulholland. Distinct Region- and Time-Dependent Functional Cortical Adaptations in C57BL/6J Mice after Short and Prolonged Alcohol Drinking. eneuro 2020, 7 (3) , ENEURO.0077-20.2020. https://doi.org/10.1523/ENEURO.0077-20.2020

    Journal of Proteome Research

    Cite this: J. Proteome Res. 2019, 18, 9, 3492–3502
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jproteome.9b00394
    Published July 22, 2019
    Copyright © 2019 American Chemical Society

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