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This gene encodes for a thiamine transporter 2 with a predominately (\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    ) central nervous system distribution. Considering that brain is particularly vulnerable to thiamine deficiency because of its reliance on thiamine pyrophosphate (\n                    <jats:styled-content style=\"fixed-case\">TPP<\/jats:styled-content>\n                    )\u2010dependent metabolic pathways involved in energy metabolism and neurotransmitter synthesis, we characterized the impact of this mutation on thiamine status, brain bioenergetics and the contribution of oxidative stress to this phenotype.\n                    <jats:italic>In silico<\/jats:italic>\n                    modeling of the mutated transporter indicated a significant loss of alpha\u2010helices resulting in a more open protein structure suggesting an impaired thiamine transport ability. The cerebral cortex and thalamus of affected dogs were severely deficient in\n                    <jats:styled-content style=\"fixed-case\">TPP<\/jats:styled-content>\n                    \u2010dependent enzymes accompanied by decreases in mitochondrial mass and oxidative phosphorylation (\n                    <jats:styled-content style=\"fixed-case\">OXPHOS<\/jats:styled-content>\n                    ) capacity, and increases in oxidative stress. These results along with the behavioral and pathological findings indicate that the phenotype associated with\n                    <jats:styled-content style=\"fixed-case\">AHE<\/jats:styled-content>\n                    is consistent with a brain\u2010specific thiamine deficiency, leading to brain mitochondrial dysfunction and increased oxidative stress. While some of the biochemical deficits, neurobehavior and affected brain areas in\n                    <jats:styled-content style=\"fixed-case\">AHE<\/jats:styled-content>\n                    were shared by\n                    <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>\n                    ernicke's and\n                    <jats:styled-content style=\"fixed-case\">K<\/jats:styled-content>\n                    orsakoff's syndromes, several differences were noted likely arising from a tissue\u2010specific vs. that from a whole\u2010body thiamine deficiency.\n                  <\/jats:p>","DOI":"10.1111\/bpa.12188","type":"journal-article","created":{"date-parts":[[2014,8,13]],"date-time":"2014-08-13T09:48:36Z","timestamp":1407923316000},"page":"441-453","source":"Crossref","is-referenced-by-count":28,"title":["Thiamine Deficiency\u2010Mediated Brain Mitochondrial Pathology in\n                    <scp>A<\/scp>\n                    laskan\n                    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