Scrg1 is induced in TSE and brain injuries, and associated with autophagy |
| |
Authors: | Dron Michel Bailly Yannick Beringue Vincent Haeberlé Anne-Marie Griffond Bernadette Risold Pierre-Yves Tovey Michael G Laude Hubert Dandoy-Dron Françoise |
| |
Institution: | CNRS UPR-9045, Laboratoire d'Oncologie Virale, 7 rue Guy Môquet BP-8, 94801 Villejuif Cedex, France; CNRS UPR-2356, Neurotransmission et Sécrétion Neuroendocrine, IFR 37 des Neurosciences, 5 rue Blaise Pascal, 67084 Strasbourg Cedex, France; Unitéde Virologie et d'Immunologie Moléculaires, INRA, 78352 Jouy-en-Josas Cedex, France; Laboratoire d'Histologie, d'Embryologie et de Cytogénétique, Facultéde Médecine et de Pharmacie, 25030 Besançon Cedex, France |
| |
Abstract: | We have previously identified Scrg1, a gene with increased cerebral mRNA levels in transmissible spongiform encephalopathies (TSE) such as scrapie, bovine spongiform encephalopathy and Creutzfeldt-Jakob disease. In this study, Scrg1-immunoreactive cells, essentially neurons, were shown to be widely distributed throughout the brain of scrapie-infected mice, while only rare and weakly immunoreactive cells could be detected in the brain of non-infected normal mice. Induction of the protein was confirmed by Western blot analysis. At the ultrastructural level, Scrg1 protein was associated with dictyosomes of the Golgi apparatus and autophagic vacuoles in the central neurons of the scrapie-infected mice. These results suggested a role for Scrg1 in the pathological changes observed in TSE. We have generated transgenic mice specifically expressing Scrg1 in neurons. No significant differences in the time course of the disease were detected between transgenic and non-transgenic mice infected with scrapie prions. However, tight association of Scrg1 with autophagic vacuoles was again observed in brain neurons of infected transgenic mice. High levels of the protein were also detected in degenerating Purkinje cells of Ngsk Prnp 0/0 mice overexpressing the Prnd gene coding for doppel, a neurotoxic paralogue of the prion protein. Furthermore, induction of Scrg1 protein was observed in the brain of mice injured by canine distemper virus or gold thioglucose treatment. Taken together, our results indicate that Scrg1 is associated with neurodegenerative processes in TSE, but is not directly linked to dysregulation of prion protein. |
| |
Keywords: | autophagic cell death neurons prion diseases Purkinje cells transgenic mice |
本文献已被 PubMed 等数据库收录! |
|