IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization
Abstract
:1. Introduction
2. Materials and Methods
2.1. Transgenic Mice
2.2. Protein Extraction
2.3. Western Blot Analysis
2.4. Histology and Immunostaining
2.5. Confocal Imaging and Image Analysis
2.6. Antibodies for Immunostaining and Immunoblotting
2.7. RNA Extraction, cDNA Synthesis, and qRT-PCR
2.8. Primary Cell Isolation and Cell Culture
2.9. Statistical Analysis
3. Results
3.1. Establishment of a Novel APP23 Mouse Model of AD (Ttg) Combined with Conditional Activation of Neuroinflammation
3.2. Astrocyte-Driven Neuroinflammation in APP23 Mice Reduces Plaque Number and Ameliorates Amyloid Plaque Burden
3.3. Expression of Enzymes Involved in APP Processing and Proteolytic Aβ Degradation Is Not Prominently Altered by Astrocytic IKK2/NF-κB Activation
3.4. Astrocytic NF-κB Activation Promotes Microglia Polarization toward a Phagocytic-Proficient Phenotype
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Microglia | In Vivo | Ex Vivo | ||||
---|---|---|---|---|---|---|
Gene Name | Mean Gene Expression | Significance | Mean Gene Expression | Significance | ||
(a) Polarization-associated | Control (Co) | IKK2-CA | EtOH | 4-OHT | ||
Cd14 | 4.859 | 7.054 | ns | 37.68 | 80.44 | * |
Cd86 | 11.22 | 13.46 | ns | 4.213 | 1.589 | ** |
Cd163 | 0.9658 | 0.3654 | ** | 0.02 | 0.0866 | * |
Inos | 0.06810 | 0.05243 | ns | na | na | na |
Mrc1 | 1.075 | 2.323 | ns | 8.459 | 0.647 | * |
Ym1 | 0.9075 | 15.39 | ** | nd | nd | nd |
(b) Inflammation-associated | Control (Co) | IKK2-CA | EtOH | 4-OHT | ||
C3 | 2.893 | 29.29 | *** | 2.15 | 155.26 | ** |
Ccl2 | 1.287 | 3.525 | ** | 0.6 | 3.32 | * |
Ccl5 | 0.1399 | 0.867 | * | 0.05 | 5.19 | ** |
Ccl6 | 17.96 | 36.8633 | ns | 44.95 | 5.992 | **** |
Gpnmb | 0.1434 | 0.8237 | ** | 3.436 | 1.156 | ns |
Gbp2 | 0.6915 | 3.618 | *** | 0.09 | 3.28 | *** |
Il1b | 7.363 | 26.35 | * | 1.22 | 92.112 | * |
Lcn2 | 4.681 | 1.710 | * | 0.06 | 262.59 | * |
Spp1 | 6.622 | 11.75 | ns | 111.4 | 27.02 | ** |
Tgfb | 73.22 | 67.22 | ns | 53.25 | 52.49 | ns |
Tgm1 | 0.1797 | 0.5212 | ** | 0.073 | 2.808 | ** |
Tnfa | 1.22 | 3.037 | * | 2.134 | 9.581 | *** |
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Yang, S.; Magnutzki, A.; Alami, N.O.; Lattke, M.; Hein, T.M.; Scheller, J.S.; Kröger, C.; Oswald, F.; Yilmazer-Hanke, D.; Wirth, T.; et al. IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization. Cells 2021, 10, 2669. https://doi.org/10.3390/cells10102669
Yang S, Magnutzki A, Alami NO, Lattke M, Hein TM, Scheller JS, Kröger C, Oswald F, Yilmazer-Hanke D, Wirth T, et al. IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization. Cells. 2021; 10(10):2669. https://doi.org/10.3390/cells10102669
Chicago/Turabian StyleYang, Shu, Alexander Magnutzki, Najwa Ouali Alami, Michael Lattke, Tabea Melissa Hein, Judith Stefanie Scheller, Carsten Kröger, Franz Oswald, Deniz Yilmazer-Hanke, Thomas Wirth, and et al. 2021. "IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization" Cells 10, no. 10: 2669. https://doi.org/10.3390/cells10102669