ASTROGLIAL REACTIVITY IN NATURAL SCRAPIE OF SHEEP

Astrogliosis is known to be a common histological feature in experimen tal scrapie, but astroglial reactivity in natural scrapie of sheep has not yet been precisely studied. We investigated the expression of two markers of glial plasticity, glial fibrillary acidic protein (GFAP) a nd glutamine synthetase (GS), by Western and Northern blotting, in dif ferent areas of the sheep brain. We report that both GFAP-mRNA and GFA P are overexpressed in the cerebellum and the pens. In the thalamus, o verexpression of GS was demonstrated for the first time in this diseas e. The enhancement of this astroglial metabolic marker, essential for glutamate and ammonia neutralization, cellular function and brain deto xification, could represent an attempt by astrocytes to maintain and c ontrol the cerebral homeostasis in this area. Our results show that as trocytes: (i) are a target for the scrapie agent even in the early tem poral evolution of the disease; (ii) react by overexpressing their int ermediate filament major protein, changing their phenotypic appearance and stabilizing their processes in precise brain areas; (iii) overexp ress key elements of their metabolism. These changes clearly implicate astrocytes in the pathogenesis of the disease.