Increased brain endothelial nitric oxide synthase expression in thiamine deficiency: relationship to selective vulnerability.
Thiamine deficiency results in selective neuronal cell death in thalamic structures. Previous studies provide evidence for a role implicating nitric oxide (NO) in the pathogenesis of cell death due to thiamine deficiency. In order to ascertain the origin of increased NO in the thiamine deficient brain, expression of endothelial nitric oxide synthase isoform (eNOS), was measured in the medial thalamus and in the inferior colliculus and compared to the frontal cortex (a spared region) of rats in which thiamine deficiency was induced through a feeding protocol of thiamine-deficient diet concomitant with daily administration of pyrithiamine, a central thiamine antagonist. eNOS mRNA and protein expression were significantly increased as a function of the severity of neurological impairment and the degree of neuronal cell loss in the medial thalamus and in the inferior colliculus. These findings suggest that the vascular endothelium is a major site of NO production in the brain in thiamine deficiency and that eNOS-derived NO could account for the selective damage to the thalamic structures that are observed in this particular disorder.
Kruse
Milarca
M
Neuroscience Research Unit, CHUM (Campus Saint-Luc), University of Montreal, 1058, Saint-Denis Street, Montreal, Que., Canada H2X 3J4.
Navarro
Darren
D
Desjardins
Paul
P
Butterworth
Roger F
RF
D000818:Animals; D001921:Brain / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000201:enzymology* / Q000235:genetics
D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat