Tags

Type your tag names separated by a space and hit enter

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

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.

Links

  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Institute of Molecular Biology, Academia Sinica, National Yang-Ming University, Taipei, Taiwan, ROC.

    , ,

    Source

    Neuroimmunomodulation 24:1 2017 pg 29-39

    MeSH

    Alzheimer Disease
    Amyloid beta-Peptides
    Amyloid beta-Protein Precursor
    Animals
    Brain
    Calcium-Binding Proteins
    Cytokines
    DNA-Binding Proteins
    Disease Models, Animal
    Exploratory Behavior
    Gene Expression Regulation
    Male
    Maze Learning
    Mice
    Mice, Inbred C57BL
    Mice, Transgenic
    Microfilament Proteins
    Microglia
    Mutation
    Presenilin-1
    Time Factors

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28618410

    Citation

    Wu, Pei-Jung, et al. "Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model." Neuroimmunomodulation, vol. 24, no. 1, 2017, pp. 29-39.
    Wu PJ, Hung YF, Liu HY, et al. Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model. Neuroimmunomodulation. 2017;24(1):29-39.
    Wu, P. J., Hung, Y. F., Liu, H. Y., & Hsueh, Y. P. (2017). Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model. Neuroimmunomodulation, 24(1), pp. 29-39. doi:10.1159/000477092.
    Wu PJ, et al. Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model. Neuroimmunomodulation. 2017;24(1):29-39. PubMed PMID: 28618410.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Deletion of the Inflammasome Sensor Aim2 Mitigates Aβ Deposition and Microglial Activation but Increases Inflammatory Cytokine Expression in an Alzheimer Disease Mouse Model. AU - Wu,Pei-Jung, AU - Hung,Yun-Fen, AU - Liu,Hsin-Yu, AU - Hsueh,Yi-Ping, Y1 - 2017/06/16/ PY - 2017/02/14/received PY - 2017/04/27/accepted PY - 2017/6/16/pubmed PY - 2018/5/10/medline PY - 2017/6/16/entrez KW - Aim2 KW - Alzheimer disease KW - Inflammasome KW - Interleukin-1 KW - Interleukin-18 KW - Interleukin-6 KW - Microglial activation KW - Neurodegenerative disorder SP - 29 EP - 39 JF - Neuroimmunomodulation JO - Neuroimmunomodulation VL - 24 IS - 1 N2 - 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. SN - 1423-0216 UR - https://www.unboundmedicine.com/medline/citation/28618410/Deletion_of_the_Inflammasome_Sensor_Aim2_Mitigates_Aβ_Deposition_and_Microglial_Activation_but_Increases_Inflammatory_Cytokine_Expression_in_an_Alzheimer_Disease_Mouse_Model_ L2 - https://www.karger.com?DOI=10.1159/000477092 DB - PRIME DP - Unbound Medicine ER -