Increased "peripheral-type" benzodiazepine receptor sites and mRNA in thalamus of thiamine-deficient rats.
"Peripheral-type" benzodiazepine receptors (PTBRs) are highly expressed on the outer mitochondrial membrane of several types of glial cells. In order to further elucidate the nature of the early glial cell changes in thiamine deficiency, PTBR sites and PTBR mRNA were measured in thalamus, a brain structure which is particularly vulnerable to thiamine deficiency, of thiamine-deficient rats at presymptomatic and symptomatic stages of deficiency. PTBR sites were measured using an in vitro binding technique and the selective radio ligand [3H]-PK11195. PTBR gene expression was measured by RT-PCR using oligonucleotide primers based upon the published sequence of the cloned rat PTBR. Microglial and astrocytic changes in thalamus due to thiamine deficiency were assessed using immunohistochemistry and antibodies to specific microglial (ED-1) and astrocytic (GFAP) proteins respectively. Significant increases of [3H]-PK11195 binding sites and concomitantly increased PTBR mRNA were observed in thalamus at the symptomatic stage of thiamine deficiency, coincident with severe neuronal cell loss and increased GFAP-immunolabelling (indicative of reactive gliosis). Positron Emission Tomography using 11C-PK11195 could provide a novel approach to the diagnosis and assessment of the extent of thalamic damage due to thiamine deficiency in humans with Wernicke's Encephalopathy.
Desjardins
P
P
Neuroscience Research Unit, CHUM (Campus Saint-Luc), Montreal, Quebec, Canada.
Todd
K G
KG
Hazell
A S
AS
Butterworth
R F
RF
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007546:Isoquinolines / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013788:Thalamus / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000235:genetics / Q000378:metabolism*; D014316:Tritium
D017931:DNA Primers; D005904:Glial Fibrillary Acidic Protein; D007546:Isoquinolines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D014316:Tritium; C037850:PK 11195