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Astroglial reactivity in natural scrapie of sheep
Affiliation:1. Department of Cell Biology & Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, State Key Laboratory of Bioactive Molecules and Druggability Assessment, MOE Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China;2. Department of Gastrointestinal Surgery & General Surgery, the Guangdong Provincial People''s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China;3. Department of Thoracic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China;4. Department of Radiation Oncology, The Fifth Hospital of Guangzhou Medical University, Guangzhou 510150, China;5. State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 519000, China;6. Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John''s University, Queens, NY 11439, USA;1. Department of Pharmacology and Physiology, Drexel University College of Medicine, Philadelphia, PA, 19102, United States;2. Department of Biology, University of São Paulo, Ribeirão Preto, São Paulo, 14040-900, Brazil
Abstract: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.
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