IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization
Alzheimer’s disease (AD) is a common neurodegenerative disease that is accompanied by pronounced neuroinflammatory responses mainly characterized by marked microgliosis and astrogliosis. However, it remains open as to how different aspects of astrocytic and microglial activation affect disease progr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| author | Shu Yang Alexander Magnutzki Najwa Ouali Alami Michael Lattke Tabea Melissa Hein Judith Stefanie Scheller Carsten Kröger Franz Oswald Deniz Yilmazer-Hanke Thomas Wirth Bernd Baumann |
| author_facet | Shu Yang Alexander Magnutzki Najwa Ouali Alami Michael Lattke Tabea Melissa Hein Judith Stefanie Scheller Carsten Kröger Franz Oswald Deniz Yilmazer-Hanke Thomas Wirth Bernd Baumann |
| author_sort | Shu Yang |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a common neurodegenerative disease that is accompanied by pronounced neuroinflammatory responses mainly characterized by marked microgliosis and astrogliosis. However, it remains open as to how different aspects of astrocytic and microglial activation affect disease progression. Previously, we found that microglia expansion in the spinal cord, initiated by IKK2/NF-κB activation in astrocytes, exhibits stage-dependent beneficial effects on the progression of amyotrophic lateral sclerosis. Here, we investigated the impact of NF-κB-initiated neuroinflammation on AD pathogenesis using the APP23 mouse model of AD in combination with conditional activation of IKK2/NF-κB signaling in astrocytes. We show that NF-κB activation in astrocytes triggers a distinct neuroinflammatory response characterized by striking astrogliosis as well as prominent microglial reactivity. Immunohistochemistry and Congo red staining revealed an overall reduction in the size and number of amyloid plaques in the cerebral cortex and hippocampus. Interestingly, isolated primary astrocytes and microglia cells exhibit specific marker gene profiles which, in the case of microglia, point to an enhanced plaque clearance capacity. In contrast, direct IKK2/NF-κB activation in microglia results in a pro-inflammatory polarization program. Our findings suggest that IKK2/NF-κB signaling in astrocytes may activate paracrine mechanisms acting on microglia function but also on APP processing in neurons. |
| first_indexed | 2024-03-10T06:39:38Z |
| format | Article |
| id | doaj.art-86b20a088cb54f49a99cefc0f3711239 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T06:39:38Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-86b20a088cb54f49a99cefc0f37112392023-11-22T17:47:16ZengMDPI AGCells2073-44092021-10-011010266910.3390/cells10102669IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia PolarizationShu Yang0Alexander Magnutzki1Najwa Ouali Alami2Michael Lattke3Tabea Melissa Hein4Judith Stefanie Scheller5Carsten Kröger6Franz Oswald7Deniz Yilmazer-Hanke8Thomas Wirth9Bernd Baumann10Institute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Clinical Neuroanatomy, Ulm University, Helmholtzstraße 8/1, 89081 Ulm, GermanyNeural Stem Cell Biology Laboratory, The Francis Crick Institute, London NW1 1AT, UKInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyCenter for Internal Medicine, Department of Internal Medicine I, University Medical Center Ulm, 89081 Ulm, GermanyInstitute of Clinical Neuroanatomy, Ulm University, Helmholtzstraße 8/1, 89081 Ulm, GermanyInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyInstitute of Physiological Chemistry, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, GermanyAlzheimer’s disease (AD) is a common neurodegenerative disease that is accompanied by pronounced neuroinflammatory responses mainly characterized by marked microgliosis and astrogliosis. However, it remains open as to how different aspects of astrocytic and microglial activation affect disease progression. Previously, we found that microglia expansion in the spinal cord, initiated by IKK2/NF-κB activation in astrocytes, exhibits stage-dependent beneficial effects on the progression of amyotrophic lateral sclerosis. Here, we investigated the impact of NF-κB-initiated neuroinflammation on AD pathogenesis using the APP23 mouse model of AD in combination with conditional activation of IKK2/NF-κB signaling in astrocytes. We show that NF-κB activation in astrocytes triggers a distinct neuroinflammatory response characterized by striking astrogliosis as well as prominent microglial reactivity. Immunohistochemistry and Congo red staining revealed an overall reduction in the size and number of amyloid plaques in the cerebral cortex and hippocampus. Interestingly, isolated primary astrocytes and microglia cells exhibit specific marker gene profiles which, in the case of microglia, point to an enhanced plaque clearance capacity. In contrast, direct IKK2/NF-κB activation in microglia results in a pro-inflammatory polarization program. Our findings suggest that IKK2/NF-κB signaling in astrocytes may activate paracrine mechanisms acting on microglia function but also on APP processing in neurons.https://www.mdpi.com/2073-4409/10/10/2669neuroinflammationAlzheimer’s diseaseNF-κBIKKastrocytesastrogliosis |
| spellingShingle | Shu Yang Alexander Magnutzki Najwa Ouali Alami Michael Lattke Tabea Melissa Hein Judith Stefanie Scheller Carsten Kröger Franz Oswald Deniz Yilmazer-Hanke Thomas Wirth Bernd Baumann IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization Cells neuroinflammation Alzheimer’s disease NF-κB IKK astrocytes astrogliosis |
| title | IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization |
| title_full | IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization |
| title_fullStr | IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization |
| title_full_unstemmed | IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization |
| title_short | IKK2/NF-κB Activation in Astrocytes Reduces amyloid β Deposition: A Process Associated with Specific Microglia Polarization |
| title_sort | ikk2 nf κb activation in astrocytes reduces amyloid β deposition a process associated with specific microglia polarization |
| topic | neuroinflammation Alzheimer’s disease NF-κB IKK astrocytes astrogliosis |
| url | https://www.mdpi.com/2073-4409/10/10/2669 |
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