Remarkable impairment of Wnt/β‐catenin signaling in the brains of the mice infected with scrapie agents

作者：Jing Sun, Hui Wang, Lina Chen, Jing Wang, Yan Lv, Xiaodong Yang, Bao‐Yun Zhang, Chan Tian, Qi Shi, Xiao‐Ping Dong · 发表于：Journal of Neurochemistry · 年份：2015 · DOI：10.1111/jnc.13416 · 被引用次数：12 · 研究领域：Prion Diseases and Protein Misfolding、Wnt/β-catenin signaling in development and cancer、Neurological diseases and metabolism

Abstract Prion diseases are a group of neurodegenerative diseases characterized by neuronal loss and spongiform degeneration, astrogliosis and aggregation of scrapie prion protein (PrP Sc ) in the central nervous system ( CNS ). The Wnt signaling pathway is a highly evolutionarily conserved pathway in eukaryotes that regulates cell proliferation, differentiation and survival. Impairment of Wnt/β‐catenin signaling has been reported in the CNS of various neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. To investigate the functional state of Wnt/β‐catenin signaling in the CNS tissues during the progression of prion disease, the components of Wnt/β‐catenin signaling in the brains of the scrapie agents 139A‐ and ME 7‐infected mice were evaluated. Compared with the normal controls, the brain levels of phosphor‐β‐catenin (Ser 33,37 and Thr 41 ) in 139A‐ and ME 7‐infected mice were significantly increased, while those of cyclin D1, which is one of the target genes of Wnt signaling, were decreased. The levels of phosphor‐glycogen synthase kinase‐3β ( GSK ‐3β) Ser 9 were markedly reduced, representing an enhanced GSK ‐3β activity in scrapie‐infected mice. Both western blot and immunohistochemical assays revealed a remarkable increase of Dickkopf‐1, the antagonist of Wnt/β‐catenin signaling, in the brains of scrapie‐infected anim‐als, which co‐localized well with the remaining neurons in the immunofluorescent tests. We also observed slightly decreased Wnt...