Thiamine deficiency induces massive cell death in the olfactory bulbs of mice.

Thiamine (vitamin B1) deficiency (TD) leads to focal brain necrosis in particular brain regions in humans and in experimental animal models. The precise mechanism of the selective topographic vulnerability triggered by TD still remains unclear. We examined the distribution pattern of cell death in the brains of mice in an experimental model of TD using anti-single-strand DNA immunohistochemistry and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling methods. We found that interneurons in the olfactory bulb were sensitive to TD. The morphologic aspects of cell death in the olfactory bulb resembled those of cell death in thalamic neurons, which have previously been examined in detail. Furthermore, cell death in the olfactory bulb was partly relieved by the administration of an N-methyl-d-aspartate receptor antagonist, as was the case in thalamic lesions by TD. The superficial part of the olfactory granule cell layer seemed to be the most sensitive to TD, suggesting that differences in the afferents between superficial and deep granule cells may influence the sensitivity of these cells to TD. Our results indicate that the olfactory bulb should be considered as one of the vulnerable regions to TD.