JAK-STAT signaling pathway mediates astrogliosis in brains of scrapie-infected mice

Scrapie is characterized histologically, in part, by astrogliosis in brain and spinal cord. However, the mechanisms of astrogliosis in brain injury occurring during prion infection are not well understood. In this study, we investigated the expression levels and cellular localization of Janus kinase (JAK) -signal transducers and activators of transcription (STAT) signaling molecules and growth factors such as leukemia inhibitory factor (LIF) and ciliary neurotropic factor (CNTF) by western blot analysis and immunohistochemistry. We found that expression levels of LIF and CNTF were increased in scrapie-infected brains and phosphorylated (p)JAK2, p-STAT1 (Ser727 and Tyr701), p-STAT3 (Tyr705), and glial fibrillary acidic protein were expressed strongly in scrapie-infected brains. Moreover, we found that p-STAT1 and p-STAT3 were found mainly in the nucleus in scrapieinfected brains. Immunohistochemically, p-STAT1 was colocalized with LIF and CNTF and p-JAK2 in many reactive astrocytes in scrapie-infected brains. In contrast, immunostaining for p-STAT3 was found in comparatively few astrocytes in limited regions; p-STAT3 staining merged with p-JAK2 in hippocampus sections of scrapie-infected brains. Taken together, our results suggest that activation of JAK2STAT1 signaling pathway occurred in reactive astrocytes in hippocampus of scrapie-infected brains.