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Thiamin deficiency and brain disorders

Published online by Cambridge University Press:  14 December 2007

Roger F. Butterworth
Roger F. Butterworth*
Affiliation:
Neuroscience Research Unit, Hôpital Saint-Luc (CHUM), 1058 St-Denis Street, Montreal, Quebec, Canada, H2X 3J4
*
Corresponding author: Dr Roger F. Butterworth, fax +1 514 412 7314, email roger.butterworth@umontreal.ca
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Abstract

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Thiamin plays a key role in the maintenance of brain function. Thiamin diphosphate is cofactor for several enzymes involved in glucose metabolism whereas thiamin triphosphate has distinct properties at the neuronal membrane. Thiamin metabolism in the brain is compartmented between neurons and neighbouring glial cells. Thiamin deficiency is commonly encountered in severe malnutrition associated with chronic alcoholism, HIV–AIDS and gastrointestinal disease where it frequently results in Wernicke's encephalopathy (the Wernicke–Korsakoff syndrome). Wernicke's encephalopathy is severely underdiagnosed according to clinical criteria in both alcoholic and HIV–AIDS patients. Magnetic resonance imaging reveals bilateral ventricular enlargement, mammillary body atrophy and cerebellar degeneration indicative of selective neuronal loss that is characteristic of Wernicke's encephalopathy. Several mechanisms have been proposed to explain this selective loss of neurons including a cerebral energy deficit resulting from reductions in activity of thiamin diphosphate-dependent enzymes, oxidative stress and N-methyl-D-aspartate receptor-mediated excitotoxicity. Both microglia and perivascular endothelial cells are sources of NO and oxidative stress in thiamin deficiency. Decreased activities of thiamin diphosphate-dependent enzymes (in particular α-ketoglutarate dehydrogenase) have also been reported in neurodegenerative diseases such as Alzheimer's and Parkinson's diseases independent of patient malnutrition. In these cases, decreased activities result from direct toxic actions of oxidative stress and β-amyloid produced as part of the neuronal cell death cascade in these disorders.

Keywords

Thiamin deficiencyWernicke–Korsakoff syndromeAlcoholismAIDSNeuronal cell death
Type
Research Article
Information
Nutrition Research Reviews , Volume 16 , Issue 2 , December 2003 , pp. 277 - 284
Copyright
Copyright © The Author 2003

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