Astrocyte gene expression in experimental mouse scrapie

The biological hallmark of transmissible spongiform encephalopathies is a significant accumulation, in brain, of the scrapie prion protein (PrPsc), often associated with an increased glial fibrillary acidic protein (GFAP) expression. This study was focused on astrocyte gene expression during scrapie development over a period of 172 days in intracerebrally inoculated newborn mice. The levels of expression of PrP and two specific astrocyte proteins, -GFAP and glutamine synthetase (GS)-, were investigated by Western and Northern blots. In brain, a 10-fold increased expression of GFAP mRNAS was demonstrated from 112 days post-inoculation to 172 days, whereas the "upregulation" of GS mRNAs was two-fold. GFAP was observed to increase 10- to 20-fold in scrapie-infected brain from day 112 to day 172, while PrP showed a three- to four-fold elevation. Both proteins were found in greater amount in the frontal cortex and cerebellum of animals with clinical scrapie than in those given an injection of normal brain. PrPsc was detected in scrapie brain from day 84 after inoculation, and thereafter increased about 20-fold until day 172. On the other hand, the concentration of glutamine synthetase remained constant in brain throughout the scrapie disease. To conclude, these results show that GFAP and GS mRNAs are differently upregulated in brain in the scrapie mouse model.