Receptor binding sites and uptake activities mediating GABA neurotransmission in chronic alcoholics with Wernicke encephalopathy.
Superior frontal cortex (SFC) and primary motor cortex tissue was obtained at autopsy from thirteen severe chronic alcoholics with neuropathologically confirmed Wernicke Encephalopathy (WE) and 22 controls. Cases with both WE and cirrhosis showed markedly fewer neurones in SFC than did WE cases without cirrhosis. The extent of the apparent neuronal loss corresponded to an increase in post-synaptic GABAA receptor sites, as assessed by the binding of [3H]muscimol to synaptic membranes. Increased [3H]muscimol binding was not accompanied by an increase in 'central-type' benzodiazepine binding sites: as assessed by [3H]flunitrazepam binding, these sites were apparently unaltered, while as assessed by [3H]diazepam binding, they were decreased. The affinities of the two benzodiazepine ligands varied differently with disease. These discrepancies between [3H]flunitrazepam and [3H]diazepam binding could not be accounted for, either by the presence of a second, diazepam-preferring, 'central-type' benzodiazepine binding site, or by loss of 'peripheral-type' sites. The changes in the post-synaptic GABAA-benzodiazepine receptor sites did not reflect any regional, disease-related deficit of afferent GABAergic terminals, as assessed by synaptosomal high-affinity [3H]GABA uptake. On a number of indices, it appears most likely that the data reflect both a loss of receptor sites, and a change in the population of receptor sub-types.
Dodd
P R
PR
John Wilson Memorial Clinical Research Laboratory, Royal Brisbane Hospital Foundation, Bancroft Centre, Qld, Australia. peterD@qimr.edu.au
Kril
J J
JJ
Thomas
G J
GJ
Watson
W E
WE
Johnston
G A
GA
Harper
C G
CG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D001665:Binding Sites; D003975:Diazepam / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism; D009118:Muscimol / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*; D014899:Wernicke Encephalopathy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018079:Receptors, GABA; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D003975:Diazepam