Journal
BRAIN RESEARCH BULLETIN
Volume 157, Issue -, Pages 10-17Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.brainresbull.2019.11.020
Keywords
Alzheimer's disease (AD); Interleukin 1 receptor (IL-1R); Amyloid beta (A beta) peptide; Neuroinflammation
Categories
Funding
- National Natural Science Foundation of China [81302781, 81471284]
- Zhejiang Provincial Natural Science Foundation of China [LQ16H010004, LY19H260003, LY20H090014]
- Zhejiang Key Technology RD Program [2017C03011]
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The neuroinflammatory response is considered a crucial event in the pathology of Alzheimer's disease (AD). Neurotoxic amyloid beta (A beta) oligomers activate neuronal glial cells, leading to the elevated generation of a large variety of inflammatory factors. Therefore, the regulation of interleukin-1 receptor (IL-1R) activity is believed to be a potential target for AD therapy. However, previous evidence of the role of IL-1R in AD-related neuroinflammation is ambiguous. To reveal the exact role of IL-1R in AD and related inflammatory reactions, we generated IL-1R(-/- )AD mice. Based on the Morris water maze results, 4-month-old IL-1R(-/- ) AD mice showed better learning and memory ability than that of AD mice. However, IL-1R(-/- ) had little influence on amyloid precursor protein proteolysis, while IL-1R(-/- ) increased ADAM17 expression level. Surprisingly, ILIL-1R(-/-) even enhanced glial activation. IL-1R(-/- ) indeed attenuated inflammatory cytokine secretion, especially that of cytokins associated with Ml polarization, while it led to increased levels of some cytokins associated with M2 polarization. Finally, we found that IL-1R(-/- ) reduced the phagocytic ability of microglia. Taken together, these results suggest that IL-1R deficiency may alleviate cognitive deficits in AD mice in a manner that is partially dependent on ADAM17 regulation and microglia M2 repolarization.
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