Region-selective alterations of glucose oxidation and amino acid synthesis in the thiamine-deficient rat brain: a re-evaluation using 1H/13C nuclear magnetic resonance spectroscopy.
Thiamine deficiency provides an effective model of selective neuronal cell death. (1)H and (13)C-NMR was used to investigate the effects of thiamine deficiency on the synthesis of amino acids derived from [1-(13)C]glucose in vulnerable (medial thalamus; MT) compared to non-vulnerable (frontal cortex; FC) brain regions. Following 11 days of thiamine deficiency, a time-point associated with the absence of significant neuronal cell death, regional concentrations of glutamate, glutamine and GABA remained unaffected in FC and MT; however, decreased levels of aspartate in MT at this time-point were a predictor of regional vulnerability. De novo synthesis of glutamate and GABA were unaffected at 11 days of thiamine deficiency, while synthesis of [2-(13)C]aspartate was significantly impaired. Glucose loading, which has been shown to exacerbate symptoms in patients with thiamine deficiency, resulted in further decreases of TCA cycle flux and reduced de novo synthesis of glutamate, aspartate and GABA in thiamine-deficient (TD) rats. Isotopomer analysis revealed that impaired TCA cycle flux and decreased aspartate synthesis due to thiamine deficiency occurred principally in neurons. Glucose loading deteriorated TD-related decreases in TCA cycle flux, and concomitantly reduced synthesis of aspartate and glutamate in MT.
Navarro
Darren
D
Neuroscience Research Unit, CHUM (Saint-Luc Hospital), University of Montreal, Montreal, Quebec, Canada.
Zwingmann
Claudia
C
Butterworth
Roger F
RF
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002247:Carbon Isotopes / Q000378:metabolism; D002952:Citric Acid Cycle / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010084:Oxidation-Reduction / Q000187:drug effects; D011745:Pyrithiamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D014316:Tritium / Q000378:metabolism
D000596:Amino Acids; D002247:Carbon Isotopes; D014316:Tritium; D011745:Pyrithiamine; D005947:Glucose