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S100a9 Knockdown Decreases the Memory Impairment and the Neuropathology in Tg2576 Mice, AD Animal Model

Cited 62 time in Web of Science Cited 69 time in Scopus
Authors
Ha, Tae-Young; Chang, Keun-A; Kim, Jeong A.; Kim, Hye-Sun; Chong, Young Hae; Suh, Yoo-Hun; Kim, Seonghan
Issue Date
2010-01-21
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE; Vol.5 1; e8840
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 APP(V717I)-CT100 transgenic mice, an animal model of AD, and isolated the S100a9 gene, which encodes an Winflammation-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 A beta 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-1 beta and TNF alpha) 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 S100a9 induced by A beta or CT contributes to cause inflammation, which then affects the neuropathology including amyloid plaques burden and impairs cognitive function. Thus, the inhibition of S100a9 is a possible target for AD therapy.
ISSN
1932-6203
Language
English
URI
https://hdl.handle.net/10371/78085
DOI
https://doi.org/10.1371/journal.pone.0008840
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College of Medicine/School of Medicine (의과대학/대학원)Pharmacology (약리학전공)Journal Papers (저널논문_약리학전공)
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