Neurotransmitter function in thiamine-deficiency encephalopathy

The encephalopathy caused by severe thiamine depletion of the mammalian CNS is accompanied by regionally selective changes in neurotransmitter function. Thiamine deficiency induced by administration of the central thiamine antagonist, pyrithiamine, causes more widespread lesions and accompanying changes in neurotransmitter function than does the deficiency state induced by chronic deprivation of the vitamin. There is convincing evidence for a central muscarinic cholinergic lesion in pyrithiamine-treated rats and neuropharmacological studies show that this lesion is partially responsible for the neurological deficit resulting from this treatment. There is also good evidence to suggest that thiamine deprivation selectively affects cerebellar afferent and efferent systems. Included in these are a loss of serotoninergic mossy fibres and of the functional integrity of glutamatergic granule cells. In addition, abnormalities of both nerve terminals and glial cells are found in lateral vestibular nucleus and it has been proposed that a loss of Purkinje cell terminals and concomitant decreases of pontine GABA may reflect these changes. The selective vulnerability of brain structures to thiamine deprivation is reflected in (i) the turnover rate of total thiamine in these areas and (ii) the selective decreases in activity of the thiamine pyrophosphate dependent enzyme pyruvate dehydrogenase.