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 st ructure which is particularly vulnerable to thiamine deficiency, of thiamin e-deficient rats at presymptomatic and symptomatic stages of deficiency. PT BR sites were measured using an in vitro binding technique and the selectiv e radio ligand [H-3]-PK11195. PTBR gene expression was measured by RT-PCR u sing oligonucleotide primers based upon the published sequence of the clone d rat PTBR. Microglial and astrocytic changes in thalamus due to thiamine d eficiency were assessed using immunohistochemistry and antibodies to specif ic microglial (ED-I) and astrocytic (GFAP) proteins respectively. Significa nt increases of [3H]-PK11195 binding sites and concomitantly increased PTBR mRNA were observed in thalamus at the symptomatic stage of thiamine defici ency, coincident with severe neuronal cell loss and increased GFAP-immunola belling (indicative of reactive gliosis). Positron Emission Tomography usin g C-11-PK11195 could provide a novel approach to the diagnosis and assessme nt of the extent of thalamic damage due to thiamine deficiency in humans wi th Wernicke's Encephalopathy. (C) 1999 Elsevier Science Ltd. All rights res erved.