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Altered Ethanol Consumption in Osteocalcin Null Mutant Mice

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Abstract

Osteocalcin (OC) is an abundant extracellular calcium-binding protein synthesized by osteoblasts. Although most OC is bound to hydroxyapatite mineral during bone formation, a consistent amount is released directly to circulation. Plasma OC (pOC) levels are highly sensitive to stressful stimuli that alter stress-responsive hormones, such as glucocorticoids (cortisol or corticosterone) and the catecholamines norepinephrine and epinephrine. To gain a better understanding of the apparent relationship of OC to the effects of ethanol (EtOH) and the stress responses, we compared mice that have OC (WT [OC+/+] and HET [OC+/−]) with OC null mutants (KO [OC−/−]), which have no OC in either plasma or in bone. One experiment included chronic unpredictable stress, a second was conducted in the absence of any known stressors other than EtOH, while a third imposed a more severe acute immobilization stress in addition to EtOH consumption. The data obtained confirmed significant differences in EtOH consumption in mice that previously experienced various stressful stimuli. We also determined that adrenal tyrosine-hydroxylase expression was inversely proportional to EtOH consumption and tended to be lower in KO than in WT. Data suggest that OC possesses the ability to modulate the adrenal gene expression of the catecholamine synthetic pathway. This modulation may be responsible for differences in EtOH consumption under stress.

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Acknowledgements

The authors would like to express their gratitude to Dr. Richard Kvetnansky for all his advice, encouragement, and friendship. Without his assistance and that of his laboratory staff, this work would not have been possible. This work was supported by grants from the National Science Foundation, SGER #0343515 and the National Institute on Alcohol Abuse and Alcoholism R21 AA 14399-01A2 (PP-B), and by funds from the Aresty Foundation for Undergraduate Research to MS and AS in partial fulfillment of requirements for Henry Rutgers Scholar awards to each.

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  1. Center of Alcohol Studies, Rutgers, The State University of New Jersey, 607 Allison Road, Piscataway, NJ, 08854, USA

    Patricia Patterson-Buckendahl, Muhammad Shahid, Ankit Shah & Larissa A. Pohorecky

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  1. Patricia Patterson-Buckendahl
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  2. Muhammad Shahid
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  3. Ankit Shah
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  4. Larissa A. Pohorecky
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Contributions

PP-B designed the experiments, prepared and wrote the manuscript. MS and AS performed all experiments, collected and analyzed data, and assisted in preparation of manuscript. LAP advised on experimental design and interpretation of manuscript.

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Correspondence to Patricia Patterson-Buckendahl.

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Research Involving Animal Rights

All protocols were reviewed and approved by the Rutgers Institutional Animal Care and Use Committee and were consistent with guidelines specified by the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

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Patterson-Buckendahl, P., Shahid, M., Shah, A. et al. Altered Ethanol Consumption in Osteocalcin Null Mutant Mice. Cell Mol Neurobiol 38, 261–271 (2018). https://doi.org/10.1007/s10571-017-0539-4

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  • DOI: https://doi.org/10.1007/s10571-017-0539-4

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