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Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo

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Abstract

Rationale

Serious neurological concomitants of alcoholism include Wernicke’s encephalopathy (WE), Korsakoff’s syndrome (KS), and hepatic encephalopathy (HE).

Objectives

This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation.

Methods

Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment.

Results

Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls.

Conclusions

These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

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Acknowledgments

This study was supported with grant funding from the NIAAA including AA005965, AA013521, and AA017168. The authors would like to acknowledge Priya Asok, Crystal Caldwell, Cheshire Hardcastle, and Matthew Serventi for their help in the data collection.

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Authors and Affiliations

  1. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 401 Quarry Rd, Stanford, CA, 94305, USA

    Natalie M. Zahr, Edith V. Sullivan & Adolf Pfefferbaum

  2. Neuroscience Program, SRI International, Menlo Park, CA, 94025, USA

    Natalie M. Zahr, Torsten Rohlfing, Dirk Mayer, Amy M. Collins & Adolf Pfefferbaum

  3. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA

    Dirk Mayer

  4. Department of Comparative Medicine, Stanford University, Stanford, CA, 94305, USA

    Richard Luong

Authors
  1. Natalie M. Zahr
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  2. Edith V. Sullivan
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  3. Torsten Rohlfing
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  4. Dirk Mayer
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  5. Amy M. Collins
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  6. Richard Luong
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  7. Adolf Pfefferbaum
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Correspondence to Natalie M. Zahr.

Ethics declarations

The Institutional Animal Care and Use Committees (IACUC) at SRI International and Stanford University approved all research protocols in accordance with the guidelines of the IACUC of the National Institute on Drug Abuse, National Institutes of Health, and the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Resources, Commission on Life Sciences, National Research Council 1996).

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The authors declare that they have no competing interest.

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Zahr, N.M., Sullivan, E.V., Rohlfing, T. et al. Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo. Psychopharmacology 233, 2675–2686 (2016). https://doi.org/10.1007/s00213-016-4313-y

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