The neurochemical pathology of thiamine deficiency: GABAA and glutamateNMDA receptor binding sites in a goat model.

Article date: 1996/3/1

PubMed ID: 2886170

Journal name: Metabolic brain disease (ISSN: 0885-7490)


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.

Author List: Dodd P R, Thomas G J, McCloskey A, Crane D I, Smith I D

Publication Types: Journal Article; Research Support, Non-U.S. Gov't

Substances mentioned in the article: Excitatory Amino Acid Antagonists; GABA Agonists; GABA Modulators; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Muscimol; gamma-Aminobutyric Acid; Flunitrazepam; Dizocilpine Maleate; Amprolium; Diazepam;

Mesh terms: Alcoholism/metabolism; Amprolium; Animals; Brain Chemistry/drug effects; Diazepam/pharmacokinetics; Disease Models, Animal; Dizocilpine Maleate/pharmacokinetics; Excitatory Amino Acid Antagonists/pharmacokinetics; Female; Flunitrazepam/pharmacokinetics; GABA Agonists/pharmacology; GABA Modulators/pharmacokinetics; Goats; In Vitro Techniques; Male; Muscimol/pharmacology; Receptors, GABA-A/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Synaptic Membranes/metabolism; Synaptosomes/metabolism; Thiamine Deficiency/chemically induced; gamma-Aminobutyric Acid/physiology;

Citations: - Muscimol binding in rat brain: association with synaptic GABA receptors.

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