Astroglial reactivity in natural scrapie of sheep

Astrogliosis is known to be a common histological feature in experimental 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) and glutamine synthetase (GS), by Western and Northern blotting, in different areas of the sheep brain. We report that both GFAP-mRNA and GFAP are overexpressed in the cerebellum and the pons. In the thalamus, overexpression of GS was demonstrated for the first time in this disease. The enhancement of this astroglial metabolic marker, essential for glutamate and ammonia neutralization, cellular function and brain detoxification, could represent an attempt by astrocytes to maintain and control the cerebral homeostasis in this area. Our results show that astrocytes: (i) are a target for the scrapie agent even in the early temporal evolution of the disease; (ii) react by overexpressing their intermediate filament major protein, changing their phenotypic appearance and stabilizing their processes in precise brain areas; (iii) overexpress key elements of their metabolism. These changes clearly implicate astrocytes in the pathogenesis of the disease.