Alcoholism: protein expression profiles in a human hippocampal model

Abstract

It is well known that chronic, excessive consumption of alcohol can cause brain damage/structural changes in the regions important for neurocognitive function. Some of the damages are permanent, while others are reversible. Molecular mechanisms underlying alcohol-induced and/or -related brain damage are largely unknown, although it is generally believed that three factors (ethanol, nutritious and hepatic factors) play important roles. Recently, we have been employing a high-throughput proteomics technology to investigate several alcohol-sensitive brain regions from uncomplicated and hepatic cirrhosis-complicated alcoholics to understand the mechanisms of alcohol effects on the CNS at the level of protein expression. The changes of protein expression profiles in the hippocampus of alcoholic subjects were firstly demonstrated using 2D gel electrophoresis-based proteomics. Protein expression profiles identified in the hippocampus of alcoholic subjects were significantly different from those previously identified by our group in other brain regions of the same alcoholic cases, possibly indicating that these different brain regions react differently to chronic alcohol ingestion at the level of protein expression. Identified changes of protein expression associated with astrocyte and oxidative stress may indicate the possibility that increased levels of CNS ammonia and reactive oxygen species induced by alcoholic mild hepatic damage/dysfunction could cause selective damage in astrocytes of the hippocampus. Although our data did not demonstrate any evidence of direct alcohol effects to induce the alteration of protein expression in association with brain damage, high-throughput neuroproteomics approaches have proved to have the potential to dissect the mechanisms of complex brain disorders. Proteomics studies on human hippocampus, an important region for neurocognitive function and psychiatric illnesses (e.g., Alzheimer’s disease, alcoholism and schizophrenia) are still sparse, and further investigation is warranted to understand the underlying mechanisms.

Keywords::

• alcohol
• brain damage
• cognition
• hippocampus
• proteomics

Acknowledgements

We thank Kimberley Kaufman (PhD student) and Mohammed Abul Kashem (Msc student) for their excellent proteomics works. Many thanks to Dr Irina Dedova, Therese Garrick, Donna Sheedy, Dr Stuart Cordwell and Ben Crossett for their advice and/or technical assistance.

Financial & competing interests disclosure

This work was supported by grants of the New South Wales (NSW) Government BioFirst Award and Australian Brewer’s Foundation, provided to Izuru Matsumoto. Human brain 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. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.