IKK2/NF-κB activation in astrocytes reduces amyloid β deposition : a process associated with specific microglia polarization
| Autor: | Yang, Shu, Magnutzki, Alexander, Alami, Najwa Ouali, Lattke, Michael, Hein, Tabea Melissa, Scheller, Judith Stefanie, Kröger, Carsten, Oswald, Franz, Yilmazer-Hanke, Deniz, Wirth, Thomas, Baumann, Bernd, Kaltschmidt, Barbara |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Hippocampus
Plaque Amyloid IκB kinase Microgliosis NF-κB neuroinflammation chemistry.chemical_compound microgliosis Gliosis Biology (General) Cells Cultured Aβ Microglia Chemistry NF-kappa B Cell Polarity Astrozyt General Medicine Astrogliosis Cell biology I-kappa B Kinase medicine.anatomical_structure Phenotype Cerebral cortex Nuklearfaktor Kappa B astrogliosis Alzheimer’s disease Signal Transduction QH301-705.5 Alzheimerkrankheit Mice Transgenic Models Biological Article Phagocytosis Alzheimer Disease medicine Animals ddc:610 Neuroinflammation Inflammation Amyloid beta-Peptides IKK medicine.disease microglia polarization Disease Models Animal Gene Expression Regulation Astrocytes Proteolysis plaque clearance DDC 610 / Medicine & health |
| Zdroj: | Cells Volume 10 Issue 10 Cells, Vol 10, Iss 2669, p 2669 (2021) |
| DOI: | 10.18725/oparu-47570 |
| Popis: | 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. publishedVersion |
| Databáze: | OpenAIRE |
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