Neuroimmunomodulation

Original Paper

Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model

Wu P.-J.a · Hung Y.-F.a, b · Liu H.-Y.a · Hsueh Y.-P.a

Author affiliations

aInstitute of Molecular Biology, Academia Sinica, and bDepartment of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan, ROC

Keywords: Aim2Alzheimer diseaseInterleukin-1Interleukin-6Interleukin-18InflammasomeMicroglial activationNeurodegenerative disorder

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Neuroimmunomodulation 2017;24:29-39
https://doi.org/10.1159/000477092

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 14, 2017
Accepted: April 27, 2017
Published online: June 16, 2017
Issue release date: August 2017

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

Abstract

Objective: Inflammation is clearly associated with Alzheimer disease (AD). Knockout of Nlrp3, a gene encoding an inflammasome sensor, has been shown to ameliorate AD pathology in a mouse model. Because AIM2 is the most dominant inflammasome sensor expressed in mouse brains, here we investigate whether Aim2 deletion also influences the phenotype of a 5XFAD AD mouse model. Methods: Quantitative RT-PCR, immunostaining, immunoblotting, and behavioral analyses were applied to compare wild-type, Aim2-/-, 5XFAD, and Aim2-/-;5XFAD mice. Results: We found that Aim2 knockout mitigates Aβ deposition in the cerebral cortex and hippocampus of 5XFAD mice. The activation of microglial cells is also reduced in Aim2-/-;5XFAD brains compared with 5XFAD brains. However, Aim2 knockout does not improve memory and anxiety phenotypes of 5XFAD mice in an open field, cued Y-maze, or Barnes maze. Compared with 5XFAD mice, Il-1 expression levels are not reduced in Aim2-/-;5XFAD mice. Unexpectedly, Il-6 and Il-18 expression levels in 5XFAD brains were further increased when Aim2 was deleted. Thus, inflammatory cytokine expression in 5XFAD brains is upregulated by Aim2 deletion through an unknown mechanism. Conclusion: Although Aim2 knockout mitigates Aβ deposition and microglial activation, Aim2 deletion does not have a beneficial effect on the spatial memory or cytokine expression of 5XFAD mice. Our findings suggest that Aβ aggregation and microglial activation may not always be correlated with the expression of inflammatory cytokines or cognitive function of 5XFAD mice. Our study also implies that different inflammasomes likely perform distinct roles in different physiological and/or pathological events.

© 2017 S. Karger AG, Basel



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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 14, 2017
Accepted: April 27, 2017
Published online: June 16, 2017
Issue release date: August 2017

Number of Print Pages: 11
Number of Figures: 5
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

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2017, Vol.24, No. 1

August 2017

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