The neurochemical pathology of thiamine deficiency: GABAA and glutamateNMDA receptor binding sites in a goat model.
Synaptic plasma membranes were prepared from four cerebrocortical areas from six male Angora goats made chronically thiamine deficient (TD) by the administration of AmproliumTM (600-900 mg/kg daily for 38-44 d). Four male controls were matched for age (27-30 mo). Four different radioligands were used to characterise GABAA and Glu-RNMDA receptor binding sites. There were marked, localised and contrasting changes in motor cortex, with an increase in GABAA and a decrease in Glu-RNMDA binding site densities. Less clearcut changes of a similar nature were seen in visual cortex. There was no variation in the parameters of GABA-activated [3H]diazepam binding between cortical areas in control goats, but there was a reduction in the maximal response to GABA in all areas in TD goats. There were regional variations in glutamate-activated [3H]MK-801 binding in control goat brain, and a non-selectively reduced maximal response in TD. Alterations in these indices of GABA- and glutamate-mediated neurotransmission may underlie the neurological signs of acute thiamine deficiency in these animals.
Dodd
P R
PR
Clinical Research Laboratory, Royal Brisbane Hospital Research Foundation, Australia.
Thomas
G J
GJ
McCloskey
A
A
Crane
D I
DI
Smith
I D
ID
D000437:Alcoholism / Q000378:metabolism / Q000473:pathology; D000670:Amprolium; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003975:Diazepam / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D018691:Excitatory Amino Acid Antagonists / Q000493:pharmacokinetics; D005260:Female; D005445:Flunitrazepam / Q000493:pharmacokinetics; D018755:GABA Agonists / Q000494:pharmacology; D018757:GABA Modulators / Q000493:pharmacokinetics; D006041:Goats; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D013574:Synaptosomes / Q000378:metabolism; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D018755:GABA Agonists; D018757:GABA Modulators; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D016291:Dizocilpine Maleate; D000670:Amprolium; D003975:Diazepam