1. Serum amyloid A inhibits astrocyte migration via activating p38 MAPK
- Author
-
Haibo Zhang, Ping Gong, Aihua Lin, Jin Liu, Yan Zhang, Yang Yu, and Yanqing Chen
- Subjects
0301 basic medicine ,Genetically modified mouse ,p38 mitogen-activated protein kinases ,animal diseases ,Immunology ,Mice, Transgenic ,p38 MAPK ,p38 Mitogen-Activated Protein Kinases ,lcsh:RC346-429 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,symbols.namesake ,Amyloid beta-Protein Precursor ,Mice ,0302 clinical medicine ,Alzheimer Disease ,Cell Movement ,Cell Line, Tumor ,mental disorders ,medicine ,Presenilin-1 ,Animals ,Humans ,Senile plaques ,Serum amyloid A ,lcsh:Neurology. Diseases of the nervous system ,Migration ,Serum Amyloid A Protein ,Chemistry ,General Neuroscience ,Research ,Colocalization ,Brain ,Golgi apparatus ,Cell biology ,Blot ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Astrocytes ,symbols ,Alzheimer’s disease ,030217 neurology & neurosurgery ,Astrocyte - Abstract
Background The accumulation of astrocytes around senile plaques is one of the pathological characteristics in Alzheimer’s disease (AD). Serum amyloid A (SAA), known as a major acute-phase protein, colocalizes with senile plaques in AD patients. Here, we demonstrate the role of SAA in astrocyte migration. Methods The effects of SAA on astrocyte activation and accumulation around amyloid β (Aβ) deposits were detected in APP/PS1 transgenic mice mated with Saa3−/− mice. SAA expression, astrocyte activation, and colocalization with Aβ deposits were evaluated in mice using immunofluorescence staining and/or Western blotting. The migration of primary cultures of mouse astrocytes and human glioma U251 cells was examined using Boyden chamber assay and scratch-would assay. The actin and microtubule networks, protrusion formation, and Golgi apparatus location in astrocytes were determined using scratch-would assay and immunofluorescence staining. Results Saa3 expression was significantly induced in aged APP/PS1 transgenic mouse brain. Saa3 deficiency exacerbated astrocyte activation and increased the number of astrocytes around Aβ deposits in APP/PS1 mice. In vitro studies demonstrated that SAA inhibited the migration of primary cultures of astrocytes and U251 cells. Mechanistic studies showed that SAA inhibited astrocyte polarization and protrusion formation via disrupting actin and microtubule reorganization and Golgi reorientation. Inhibition of the p38 MAPK pathway abolished the suppression of SAA on astrocyte migration and polarization. Conclusions These results suggest that increased SAA in the brain of APP/PS1 mice inhibits the migration of astrocytes to amyloid plaques by activating the p38 MAPK pathway.
- Published
- 2020