Increased densities of binding sites for the "peripheral-type" benzodiazepine receptor ligand [3H]PK11195 in vulnerable regions of the rat brain in thiamine deficiency encephalopathy.
Quantitative receptor autoradiography was used to evaluate the density of high-affinity binding sites for the "peripheral-type" benzodiazepine receptor (PTBR) ligand [3H]PK11195 in brain regions of the rat at different stages of pyrithiamine-induced thiamine deficiency encephalopathy, an experimental model of the Wernicke-Korsakoff syndrome (WKS). Assessment of the density of [3H]PK11195 binding sites in thiamine-deficient animals showing no neurologic signs of thiamine deficiency encephalopathy, and revealed no significant alterations compared with pair-fed control animals in any brain region studied. Densities of [3H]PK11195 binding sites were, however, significantly increased in brain regions of the rat at the symptomatic stage, where increased densities were seen in the inferior colliculus (233% increase, p < 0.001), inferior olivary nucleus (154% increase, p < 0.001) and thalamus (up to 107% increase, p < 0.001). Histologic studies of these same brain regions revealed evidence of neuronal cell loss and concomitant gliosis. Densities of [3H]PK11195 binding sites in nonvulnerable brain regions that showed no histologic evidence of neuronal loss, such as the cerebral cortex, hippocampus, and caudate-putamen, were not significantly different from those in control animals. Increased densities of binding sites for the PTBR ligand probably reflect glial proliferation and are consistent with an excitotoxic mechanism in the pathogenesis of neuronal cell loss in thiamine deficiency encephalopathy. Positron emission tomography (PET) using [11C]PK11195 could offer a potentially useful diagnostic tool in WKS in humans.
Leong
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DK
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, Canada.
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Oliva
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Butterworth
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RF
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001927:Brain Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D007546:Isoquinolines / Q000378:metabolism*; D008024:Ligands; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000150:complications*; D014316:Tritium
D007546:Isoquinolines; D008024:Ligands; D011963:Receptors, GABA-A; D014316:Tritium; C037850:PK 11195