Role of GFAP in morphological retention and distribution of reactive astrocytes induced by scrapie encephalopathy in mice

We have previously demonstrated that mutant mice bearing astrocytes deficient in glial fibrillary acidic protein (GFAP) exhibited typical spongiform degeneration and prion plaque deposition. However, it remains to be determined whether there are astrocyte-specific alterations in the reactive response of astrocytes. Herein, we analyzed morphological features of Gfap(-/-) reactive astrocytes. Light microscopic morphometry of mutant reactive astrocytes revealed reduced outlined cell area and shorter distances among expanded cell space but with larger nuclei. Electron microscopy revealed mutant cells containing very few and sparse glial filaments as well as abnormal cytoarchitecture of reactive astrocytic processes. Furthermore, paired cell formation appeared frequently. The results suggest that GFAP is necessary for morphological retention and distribution of reactive astrocytes during prion disease, and that there is a GFAP-dependent function of glial filaments in reactive astrocytes. (C) 2009 Elsevier B.V. All rights reserved.