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Cerebellar Vermis Proteome of Chronic Alcoholic Individuals

Authors


  • This work was supported by grants from the NSW Government BioFirst Award and Australian Brewer's Foundation, provided to IM. KA-K is an Australian Postgraduate Award holder. 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.

Reprint requests: Izuru Matsumoto, Discipline of Pathology, Faculty of Medicine, The University of Sydney, NSW 2006, Australia; Fax: +612-9351-3429; E-mail: izuru@med.usyd.edu.au

Abstract

Background: Cerebellar changes are commonly associated with alcoholism and chronic alcohol consumption can produce profound impairments in motor functioning and various aspects of cognition. Although the mechanisms underlying alcohol-induced changes in the cerebellar vermis are poorly understood, observations in the alcoholic vermis are thought to be consequential to common alcohol-related factors, particularly thiamine deficiency.

Methods: In the present study, we used a proteomics-based approach to compare protein expression profiles of the cerebellar vermis from human alcoholic individuals (both neurologically uncomplicated and alcoholic individuals complicated with liver cirrhosis) and healthy control brains. This article complements our recent studies performed on alcoholic prefrontal gray and white matter and splenium of the corpus callosum (CC).

Results: Like the CC study, several liver cirrhosis-specific proteins were identified in the vermis, perhaps indicating the effects of liver dysfunction in this brain region. Among other protein expression changes observed are disturbances in the levels of thiamine-dependent enzymes. A derangement in energy metabolism perhaps related to thiamine deficiency seems to be important in both alcoholic groups, even where there are no clinical or pathological findings of Wernicke–Korsakoff syndrome.

Conclusions: These results suggest that clinically and pathologically uncomplicated alcoholic cases may not in fact be “uncomplicated,” as at the proteome level we seem to be isolating the confounding effects of nutritional deficiencies and liver dysfunction and perhaps their role in alcohol-related vermis damage. Together, these results indicate that the alcohol-related pathology of the vermis is more multifactorial than other brain regions examined previously (prefrontal region and CC splenium).

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