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Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study

Molecular Psychiatry volume 11, pages 56–65 (2006)Cite this article

Abstract

Neuroimaging and post-mortem studies indicate that chronic alcohol use induces global changes in brain morphology, such as cortical and subcortical atrophy. Recent studies have shown that frontal lobe structures are specifically susceptible to alcohol-related brain damage and shrinkage in this area is largely due to a loss of white matter. This may explain the high incidence of cognitive dysfunction observed in alcoholics. Using a proteomics-based approach, changes in protein expression in the dorsolateral prefrontal region (BA9) white matter were identified in human alcoholic brains. Protein extracts from the BA9 white matter of 25 human brains (10 controls; eight uncomplicated alcoholics; six alcoholics complicated with hepatic cirrhosis; one reformed alcoholic) were separated using two-dimensional gel electrophoresis. Overall, changes in the relative expression of 60 proteins were identified (P<0.05, ANOVA) in the alcoholic BA9 white matter. In total, 18 protein spots have been identified using MALDI-TOF; including hNP22, α-internexin, transketolase, creatine kinase chain B, ubiquitin carboxy-terminal hydrolase L1 and glyceraldehyde-3-phosphate dehydrogenase. Several of these proteins have been previously implicated in alcohol-related disorders and brain damage. By identifying changes in protein expression in this region from alcoholics, hypotheses may draw upon more mechanistic explanations as to how chronic ethanol consumption causes white matter damage.

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Acknowledgements

Tissues were received from the NSW Tissue Resource Centre, which is supported by the University of Sydney, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health. We thank Ms Therese Garrick and Ms Alisa Green for their advice and the Biomedical Mass Spectrometry Facility, University of New South Wales for their technical assistance. This work was supported by grants of the NSW Government BioFirst Award and Australian Brewer's Foundation, provided to IM. KA is an Australian Postgraduate Award holder.

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  1. Department of Pathology, The University of Sydney, NSW, Australia

    K Alexander-Kaufman, G James, D Sheedy, C Harper & I Matsumoto

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Correspondence to I Matsumoto.

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Alexander-Kaufman, K., James, G., Sheedy, D. et al. Differential protein expression in the prefrontal white matter of human alcoholics: a proteomics study. Mol Psychiatry 11, 56–65 (2006). https://doi.org/10.1038/sj.mp.4001741

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