s100a9 knockdown decreases the memory impairment and the neuropathology in tg2576 mice, ad animal models100a9击倒减少tg2576小鼠记忆障碍和神经病理学,ad动物模型.pdfVIP

S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model 1. 1. 1 1 1 2 Tae-Young Ha , Keun-A Chang , Jeong a Kim , Hye-Sun Kim , Seonghan Kim , Young Hae Chong , Yoo-Hun Suh1* 1 Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer’s Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea, 2 Department of Microbiology, School of Medicine, Ewha Womans University, Yangcheonku, Seoul, South Korea Abstract Inflammation, insoluble protein deposition and neuronal cell loss are important features in the Alzheimer’s disease (AD) brain. To investigate the regulatory genes responsible for the neuropathology in AD, we performed microarray analysis with APPV717I-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an inflammation- associated calcium binding protein. In another AD animal model, Tg2576 mouse brain, and in human AD brain, induction of S100a9 was confirmed. The endogenous expression of S100a9 was induced by treatment with Ab or CT peptides in a microglia cell line, BV2 cells. In these cells, silencing study of S100a9 showed that the induction of S100a9 increased the intracellular calcium level and up-regulated the inflammatory cytokines (IL-1b and TNFa) and iNOS. S100a9 lentiviral short hairpin RNA (sh-S100a9) was injected into the hippocampus region of the brains of 13-month-old Tg2576 mice. At two months after injection, we found that knockdown of S100a9 expression had improved the cognition decline of Tg2576 mice in the water maze task, and had reduced amyloid plaque burden. These results suggest that S1