Downregulation of canonical Wnt signaling in hippocampus of SAMP8 mice.

摘要: Abstract In the adult brain, canonical Wnt (Wnt/β-catenin) signaling modulates neuronal function, hippocampal neurogenesis, and synaptic plasticity. Indeed, growing evidence suggests that downregulation of could be involved in cognitive decline associated with aging also physiopathology Alzheimer's disease (AD). However, molecular basis remains unknown. At present, SAMP8 is an experimental model has been proposed for studying age-related neurodegenerative changes pathogenesis AD. Here, we examined hippocampus mice at 9 12 months age, as well its control-strain SAMR1 mice. Our results showed increased Dickkopf-1 protein levels addition to GSK-3 α/β activation hyperphosphorylated tau. Consequently, higher β-catenin phosphorylation Ser33,37 Thr41, which promotes degradation, along a decrease active (ABC) nucleus, were observed SAMP8, mainly age 12 months. Moreover, nuclear Dvl3 lower 9- 12-month-old Related these findings, increase loss was antiapoptotic target gene, Bcl-2, proapototic Bax. suggest relationship between Thus, enhancing may represent novel neuroprotective strategy aimed counteracting not only but