title: S100A9 knockout decreases the memory impairment and neuropathology in crossbreed mice of Tg2576 and S100A9 knockout mice model.
abstract: Our previous study presented evidence that the inflammation-related S100A9 gene is significantly upregulated in the brains of Alzheimer's disease (AD) animal models and human AD patients. In addition, experiments have shown that knockdown of S100A9 expression improves cognition function in AD model mice (Tg2576), and these animals exhibit reduced amyloid plaque burden. In this study, we established a new transgenic animal model of AD by crossbreeding the Tg2576 mouse with the S100A9 knockout (KO) mouse. We observed that S100A9KO/Tg2576 (KO/Tg) mice displayed an increased spatial reference memory in the Morris water maze task and Y-maze task as well as decreased amyloid beta peptide (Aβ) neuropathology because of reduced levels of Aβ, C-terminal fragments of amyloid precursor protein (APP-CT) and phosphorylated tau and increased expression of anti-inflammatory IL-10 and also decreased expression of inflammatory IL-6 and tumor neurosis factor (TNF)-α when compared with age-matched S100A9WT/Tg2576 (WT/Tg) mice. Overall, these results suggest that S100A9 is responsible for the neurodegeneration and cognitive deficits in Tg2576 mice. The mechanism of S100A9 is able to coincide with the inflammatory process. These findings indicate that knockout of S100A9 is a potential target for the pharmacological therapy of AD.
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea ; Korea Brain Research Institute (KBRI), Daegu, South Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gachon University of Medicine and Science, Incheon, South Korea.
authors.forename: Keun-A
authors.initials: KA
authors.lastname: Chang
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.
authors.forename: Jeonga
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, Gachon University of Medicine and Science, Incheon, South Korea.
authors.forename: Sungji
authors.initials: S
authors.lastname: Ha
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.
authors.forename: Ki-Young
authors.initials: KY
authors.lastname: Shin
authors.affiliation: Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu, South Korea.
authors.forename: Cheil
authors.initials: C
authors.lastname: Moon
authors.affiliation: Institute of Molecular Virology, Centre of Molecular Biology of Inflammation, Westfälische Wilhelms University Münster, Münster, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nacken
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Medicine, Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea ; Korea Brain Research Institute (KBRI), Daegu, South Korea.
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
mesh_terms: D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism; D000818:Animals; D040502:Calgranulin B / Q000235:genetics* / Q000378:metabolism; D003072:Cognition Disorders / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008569:Memory Disorders / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism; D008822:Mice, Transgenic / Q000235:genetics / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D040502:Calgranulin B; D015850:Interleukin-6; C576329:S100A9 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10