Glucose loading precipitates focal lactic acidosis in the vulnerable medial thalamus of thiamine-deficient rats.
Glucose loading in thiamine-deficient patients is known to precipitate Wernicke's Encephalopathy; however, the mechanisms responsible have not been fully elucidated. Lactate accumulation occurs in brains of thiamine-deficient rats. In order to determine whether glucose loading in thiamine-deficient rats causes selective lactic acidosis in vulnerable brain structures, cerebral pH was measured autoradiographically using 14-labeled 5,5-dimethyloxazolidine-2, 4-dione ([(14)C]DMO) in the medial thalamus, a vulnerable brain region, versus cerebral cortex, a brain region that is spared in thiamine deficiency. Following administration of a glucose load, regional lactate levels and de novo lactate synthesis measured by (1)H-(13)C-NMR spectroscopy, increased significantly to 21.86 +/- 3.04 mumol/g (wet weight) in the medial thalamus (p < 0.001) and pH in this brain region was decreased significantly from 7.08 +/- 0.04 to 6.87 +/- 0.05 (p < 0.001). No such changes were observed in cerebral cortex following a glucose load. These results demonstrate that the increased production and accumulation of brain lactate result in acidosis following glucose loading in thiamine deficiency. Alterations of brain pH could contribute to the pathogenesis of thalamic neuronal damage and consequent cerebral dysfunction in Wernicke's Encephalopathy.
Navarro
Darren
D
Neuroscience Research Unit, CHUM (Campus Saint-Luc), University of Montreal, 1058 Saint-Denis Street, Montreal, Quebec, Canada.
Zwingmann
Claudia
C
Chatauret
Nicolas
N
Butterworth
Roger F
RF
D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects; D004114:Dimethadione; D005947:Glucose / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism* / Q000473:pathology; D013832:Thiamine Deficiency / Q000378:metabolism* / Q000473:pathology
D019275:Radiopharmaceuticals; D004114:Dimethadione; D005947:Glucose