A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques

Christa Helms, Ilhem Messaoudi, Sophia Jeng, Willard M. Freeman, Kent E. Vrana, Kathleen (Kathy) Grant

    Research output: Contribution to journalArticle

    23 Citations (Scopus)

    Abstract

    Background: Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods: Plasma proteins (n=60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n=10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4months, and after 12months of 22-hour daily concurrent access to ethanol and water. Results: Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusions: Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity.

    Original languageEnglish (US)
    Pages (from-to)995-1003
    Number of pages9
    JournalAlcoholism: Clinical and Experimental Research
    Volume36
    Issue number6
    DOIs
    StatePublished - Jun 2012

    Fingerprint

    Self Administration
    Macaca
    Heat-Shock Proteins
    Ethanol
    Adrenocorticotropic Hormone
    Primates
    Janus Kinases
    Hydrocortisone
    Blood Proteins
    Proteins
    Macaca fascicularis
    Transcription
    Transducers
    Water
    Hormones
    Alcoholics
    B-Lymphocytes
    Cells
    Light
    Experiments

    Keywords

    • Adrenocorticotropic Hormone
    • Cortisol
    • Ethanol
    • Luminex
    • Nonhuman Primates

    ASJC Scopus subject areas

    • Medicine (miscellaneous)
    • Psychiatry and Mental health
    • Toxicology

    Cite this

    A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques. / Helms, Christa; Messaoudi, Ilhem; Jeng, Sophia; Freeman, Willard M.; Vrana, Kent E.; Grant, Kathleen (Kathy).

    In: Alcoholism: Clinical and Experimental Research, Vol. 36, No. 6, 06.2012, p. 995-1003.

    Research output: Contribution to journalArticle

    Helms, Christa ; Messaoudi, Ilhem ; Jeng, Sophia ; Freeman, Willard M. ; Vrana, Kent E. ; Grant, Kathleen (Kathy). / A Longitudinal Analysis of Circulating Stress-Related Proteins and Chronic Ethanol Self-Administration in Cynomolgus Macaques. In: Alcoholism: Clinical and Experimental Research. 2012 ; Vol. 36, No. 6. pp. 995-1003.
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    AU - Vrana, Kent E.

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    AB - Background: Alcoholics have alterations in endocrine and immune functions and increased susceptibility to stress-related disorders. A longitudinal analysis of chronic ethanol intake on homeostatic mechanisms is, however, incompletely characterized in primates. Methods: Plasma proteins (n=60; Luminex) and hormones (adrenocorticotropic hormone [ACTH]; cortisol) were repeatedly measured in adult male cynomolgus monkeys (Macaca fascicularis, n=10) during a 32-month experimental protocol at baseline, during induction of water and ethanol (4% w/v in water) self-administration, after 4months, and after 12months of 22-hour daily concurrent access to ethanol and water. Results: Significant changes were observed in ACTH, cortisol, and 45/60 plasma proteins: a majority (28/45) were suppressed as a function of ethanol self-administration, 8 proteins were elevated, and 9 showed biphasic changes. Cortisol and ACTH were greatest during induction, and correlations between these hormones and plasma proteins varied across the experiment. Pathway analyses implicated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) as possible mediators of ethanol-induced effects on immune-related proteins in primates. Conclusions: Chronic ethanol consumption in primates leads to an allostatic state of physiological compromise with respect to circulating immune- and stress-related proteins in NF-κB- and STAT/JAK-related pathways in correlation with altered endocrine activity.

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