{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:01:29Z","timestamp":1789585289816,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2001,12,20]],"date-time":"2001-12-20T00:00:00Z","timestamp":1008806400000},"content-version":"vor","delay-in-days":141,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2001,8]]},"abstract":"<jats:p>Although earlier studies on thiamine deficiency have reported increases in extracellular glutamate concentration in the thalamus, a vulnerable region of the brain in this disorder, the mechanism by which this occurs has remained unresolved. Treatment with pyrithiamine, a central thiamine antagonist, resulted in a 71 and 55% decrease in protein levels of the astrocyte glutamate transporters GLT\u20101 and GLAST, respectively, by immunoblotting in the medial thalamus of day\u200314 symptomatic rats at loss of righting reflexes. These changes occurred prior to the onset of convulsions and pannecrosis. Loss of both GLT\u20101 and GLAST transporter sites was also confirmed in this region of the thalamus at the symptomatic stage using immunohistochemical methods. In contrast, no change in either transporter protein was detected in the non\u2010vulnerable frontal parietal cortex. These effects are selective; protein levels of the astrocyte GABA transporter GAT\u20103 were unaffected in the medial thalamus. In addition, astrocyte\u2010specific glial fibrillary acidic protein (GFAP) content was unchanged in this brain region, suggesting that astrocytes are spared in this disorder. Loss of GLT\u20101 or GLAST protein was not observed on day\u200312 of treatment, indicating that down\u2010regulation of these transporters occurs within 48\u2003h prior to loss of righting reflexes. Finally, GLT\u20101 content was positively correlated with levels of the neurofilament protein \u03b1\u2010internexin, suggesting that early neuronal drop\u2010out may contribute to the down\u2010regulation of this glutamate transporter and subsequent pannecrosis. A selective, focal loss of GLT\u20101 and GLAST transporter proteins provides a rational explanation for the increase in interstitial glutamate levels, and may play a major role in the selective vulnerability of thalamic structures to thiamine deficiency\u2010induced cell death.<\/jats:p>","DOI":"10.1046\/j.1471-4159.2001.00436.x","type":"journal-article","created":{"date-parts":[[2003,3,12]],"date-time":"2003-03-12T06:55:26Z","timestamp":1047452126000},"page":"560-568","source":"Crossref","is-referenced-by-count":76,"title":["Selective down\u2010regulation of the astrocyte glutamate transporters GLT\u20101 and GLAST within the medial thalamus in experimental Wernicke's encephalopathy"],"prefix":"10.1111","volume":"78","author":[{"given":"Alan S.","family":"Hazell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. V. 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