Neuropathological alterations in alcoholic brains. Studies arising from the New South Wales Tissue Resource Centre

Abstract

Alcohol dependence and abuse are among the most costly health problems in the world from both social and economic points of view. Patterns of drinking appear to be changing throughout the world with more women and young people drinking heavily. Excessive drinking can lead to impairment of cognitive function and structural brain changes—some permanent, some reversible. Patterns of damage appear to relate to lifetime alcohol consumption but, more importantly, to associated medical complications. The most significant of these is the alcohol-related vitamin deficient state, the Wernicke–Korsakoff syndrome (WKS), which is caused by thiamin deficiency but is seen most commonly in alcoholics. Careful selection and classification of alcoholic cases into those with and without these complications, together with detailed quantitative neuropathological analyses has provided data that gives clues to the most vulnerable regions and cells in the brain. Brain shrinkage is largely accounted for by loss of white matter. Some of this damage appears to be reversible. Alcohol-related neuronal loss has been documented in specific regions of the cerebral cortex (superior frontal association cortex), hypothalamus and cerebellum. No change is found in basal ganglia, nucleus basalis, or serotonergic raphe nuclei. Many of these regions which are normal in uncomplicated alcoholics are damaged in those with the WKS. Dendritic and synaptic changes have been documented in alcoholics and these, together with receptor and transmitter changes, may explain functional changes and cognitive deficits, which precede more severe structural neuronal changes. A resource to provide human brain tissues for these types of studies has been developed at the University of Sydney—the New South Wales Tissue Resource Centre. The aim of this facility is to provide research groups throughout the world with fresh and/or frozen tissues from well-characterized cases of alcohol-related brain damage and matched controls. The development of new technologies in pathology and molecular biology means that many more questions can be addressed using appropriately stored human brain tissues. Examples of the application of some of these techniques, involving neurochemical, neuropharmacological, neuroimaging and gene expression studies are included in this paper. Important public health outcomes have arisen from some of these studies including the enrichment of bread flour with thiamin for the whole of Australia. Researchers with an interest in alcohol studies can access tissues from this brain bank.