• Qian Xiao, Weihua Yu, Qi Tian, Xue Fu, Xia Wang, Min Gu, and Yang Lü.
• Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
• Neuroscience. 2017 Jul 4; 355: 61-70.

AbstractChitinase activity is increased in Alzheimer's disease (AD). However, the role of chitinase1 in AD is unknown. We investigated the effects of chitinase1 on Alzheimer's pathology and microglia function. Artificial chitinase1 and chitinase inhibitor (chitinase-IN-2) were used to determine the effects of chitinase1 on inflammatory factors and β-amyloid (Aβ) oligomers deposition in D-galactose/AlCl3-induced rat model with cognitive impairments. Aβ-treated N9 microglia cells were analyzed to further verify whether the changes in inflammatory factors following chitinase1 treatment were associated with microglia alternative activation. Our data displayed that the activity of chitinase1 was both improved in D-galactose/AlCl3-injected rats and Aβ-pretreated microglia. Moreover, there was an improvement in cognitive function in chitinase1-treated AD rats. Furthermore, anti-inflammation factors (Arginase 1, Arg-1, mannose receptor type C 1, MRC1/CD206) were increased and pro-inflammation factors (tumor necrosis factor alpha, TNFα, interleukin 1 beta, IL-1β) were decreased in D-galactose/AlCl3-induced AD rats with chitinase1 treatment. A higher level of M2 markers (Arg-1, MRC1/CD206) and a lower level of classic M1 markers (TNFa, IL-1β) were obtained in Aβ-pretreated N9 cells with chitinase1, suggesting that chitinase1 polarized the microglia into an anti-AD M2 phenotype. We also detected that chitnase1 could weaken the deposition of Aβ oligomers in the brain of D-galactose/ AlCl3-induced AD rats. In conclusion, Chitinase1 might exert protective effects against AD by polarizing microglia to an M2 phenotype and resisting Aβ oligomer deposition.Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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