Brain lactate synthesis in thiamine deficiency: a re-evaluation using 1H-13C nuclear magnetic resonance spectroscopy.
Region-selective accumulation of brain lactate occurs in TD; however, the mechanisms responsible have not been elucidated fully. (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy were therefore used to investigate de novo lactate synthesis from [1-(13)C]glucose in vulnerable (medial thalamus) and nonvulnerable (frontal cortex) brain regions of rats made thiamine deficient by administration of the central thiamine antagonist pyrithiamine. De novo synthesis of lactate was increased in the medial thalamus to 148% and 226% of pair-fed control values at presymptomatic and symptomatic stages of thiamine deficiency, respectively, whereas no such changes were observed in the frontal cortex. Administration of a glucose load selectively worsened the changes in medial thalamus. Pyruvate recycling and peripherally derived lactate did not contribute significantly to the lactate increase within the thiamine-deficient brain. Increases in immunolabeling of the lactate dehydrogenase isoenzymes (LDH1 and LDH5) were observed in the medial thalamus of thiamine-deficient animals. Metabolic impairment due to thiamine deficiency thus results in increased glycolysis, increased LDH immunolabeling of neurons and astrocytes and increased de novo synthesis of lactate in brain regions vulnerable to thiamine deficiency. These results are consistent with the notion that focal lactate accumulation participates in the worsening of neurologic symptoms in thiamine-deficient patients.
Navarro
Darren
D
Neuroscience Research Unit, CHUM (Campus Saint-Luc), University of Montreal, 1058 Saint-Denis Street, Montreal, Province of Quebec H2X 3J4, Canada.
Zwingmann
Claudia
C
Hazell
Alan S
AS
Butterworth
Roger F
RF
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects; D002247:Carbon Isotopes / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005069:Evaluation Studies as Topic; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D007527:Isoenzymes / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008954:Models, Biological; D011745:Pyrithiamine; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism
D002247:Carbon Isotopes; D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D014316:Tritium; D019344:Lactic Acid; D011745:Pyrithiamine; D019289:Pyruvic Acid; D007770:L-Lactate Dehydrogenase; C409667:lactate dehydrogenase 1; D005947:Glucose