Progress in Neuro-Psychopharmacology and Biological Psychiatry
Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre
Introduction
Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Alcohol is considered a factor in diseases such as cancer, liver and heart disease and 20–40% of patients in large urban hospitals are there because of illnesses that have been caused or made worse by drinking. Seven percent of the adult American population are said to have alcohol-related problems and approximately 40 million may be directly or indirectly affected by alcoholism. Alcohol dependence and abuse in the United States is estimated to cost US$184.6 billion annually (Gordis, 2000). The consequences of excessive and underage drinking affect virtually all college campuses, their students and their communities Hingson et al., 2002, Wechsler et al., 2002. The consumption of alcohol in Australia is higher than in the United States and ranks 20th overall (7.5 l per capita per annum of absolute alcohol) (Verhoek, 1997). However, this is significantly less than equivalent figures in the 1980s when Australians were drinking 9.7 l per capita per annum. Sixty-six percent of Australian males and 43% of females drink alcohol and, of these 14% of males and 2% of females drink at levels considered hazardous to health (Wodak, 1986). In a more recent Australian study of female drinkers, 34% were classified as hazardous drinkers, 4% as harmful and 1% as dependent (Fleming, 1996). Binge drinking is a major problem in young women in Australia (Jonas et al., 2000). Similar alcohol-related problems are seen in most other countries in the world including the Asia-Pacific region (Cho et al., 2002). Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily.
Scientists have begun to unravel the complex interrelationships of alcohol-related brain damage. There is little doubt that excessive consumption of alcohol can lead to impairment of cognitive function. Clinical and neuropsychological data certainly point towards such an entity (Oscar-Berman and Hutner, 1993) and neuroimaging techniques have demonstrated structural and functional abnormalities in apparently uncomplicated alcoholics who are cognitively impaired Melgaard et al., 1990, Pfefferbaum et al., 1997. A significant difficulty in studying the long-term effects of alcohol on the brain are associated medical complications—specifically, alcohol-induced cirrhosis of the liver and alcohol-related nutritional vitamin deficiency states such as pellagra and the Wernicke–Korsakoff Syndrome (WKS). WKS is caused by thiamin deficiency but is seen most commonly in alcoholics (Harper et al., 1995). These disorders are also known to cause cognitive dysfunction and it is important to identify these if one is studying the effects of alcohol on the brain using human brain bank material.
The development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues Cairns and Lantos, 1996, Bell and Ironside, 1997. It is possible to detect and measure genes, proteins and chemical changes in the brain that were not even imagined 10 years ago. Recent international scientific progress in the study of alcohol-related brain damage Lewohl et al., 2000, Lewohl et al., 2001, Matsumoto et al., 2001b attest to the success of the application of many of these techniques using autopsy tissues. A resource to provide autopsy tissues for these types of studies has been developed at the University of Sydney. The main focus of the New South Wales Tissue Resource Centre (TRC) is alcohol-related brain damage and the aim is to provide tissues (fresh-frozen and formalin-fixed) to research groups throughout the world Harper et al., 2002, Sarris et al., 2002. Some of the scientific outcomes arising from the use of these materials are discussed herein.
Section snippets
Resource material
The Department of Neuropathology in the Central Sydney Area Health Service and the University of Sydney provides a referral service for the state of New South Wales (population 6.8 million). This includes all the major teaching hospitals of Sydney and the Department of Forensic Medicine (Coroner's Office). Approximately 3000 autopsies per year are performed at the Department of Forensic Medicine in Central Sydney. A long-standing interest in alcohol-related brain damage has meant that many
Neuropathology studies
Brain weight studies showed that alcoholics have a reduced brain weight compared to controls (Harper and Blumbergs, 1982). A correlation between the degree of brain atrophy and the rate and amount of alcohol consumed over a lifetime has been noted (Harding et al., 1996). The reduction in brain weight and volume is largely accounted for by a reduction in the white matter volume. A significant age effect in both control and alcoholic groups suggests a possible relationship between aging and
Conclusion
An important aim of this paper is to alert research scientists to the fact that brain tissues from people with alcohol-related disorders are available and can be used for a wide range of structural and molecular techniques. The adult human brain weighs 1.2–1.6 kg, but dynamic experiments typically require only 1–5 g of tissue and molecular studies much less, so that a single case can provide material for many experiments. Most enzymes are quite stable in autopsy tissue Hardy and Dodd, 1983,
Acknowledgements
The NSW Tissue Resource Centre is supported by The University of Sydney, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism Grant: R24 AA12725 and the NSW Department of Health. We would like to thank the researchers who have supported the NSW Tissue Resource Centre. Special thanks go to Drs. Dodd, Lewohl, Wilce, Pfefferbaum and Sullivan, for their input into the sections dealing with uses of brain bank tissues for neuropharmacology,
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2019, Clinics in Liver DiseaseCitation Excerpt :In addition, alcoholic dementia presents earlier than other acquired forms of dementia.3 The CNS atrophy that has been linked to alcoholic neurodegeneration is caused by destruction of myelin and loss of dendritic connections as well as neuronal loss.27 This loss occurs most prominently in the prefrontal regions and corpus callosum, and occurs independently from thiamine deficiency.8,51