Serum amyloid A inhibits astrocyte migration via activating p38 MAPK
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RESEARCH
Open Access
Serum amyloid A inhibits astrocyte migration via activating p38 MAPK Aihua Lin1†, Jin Liu1,2†, Ping Gong1, Yanqing Chen1, Haibo Zhang1, Yan Zhang1 and Yang Yu1*
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. Keywords: Alzheimer’s disease, Serum amyloid A, Astrocytes, Migration, p38 MAPK
Background Alzheimer’s disease (AD), the major cause of dementia in the elderly, is a chronic progressive neurodegenerative disorder [1]. One of the major neuropathological features of AD is the accumulation of extracellular senile plaques composed of aggregated amyloid β (Aβ). Aggregated Aβ has been proved to play a key role in the * Correspondence: [email protected] † Aihua Lin and Jin Liu contributed equally to this work. 1 Engineering Research Center of Cell and Therapeutic Antibody, Ministry of Education, and School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China Full list of author information is available at the end of the article
occurrence and progression of AD [2, 3]. Besides, neuroinflammation has also been found to contribute to AD [4]. Astrocytes, the most abundant neuroglial cells in the mammalian brain, are involved in AD-related neuroinflammation. Astrocytes are activated in AD and have been found in large numbers to colocalize with and surround Aβ plaques [5, 6]. At the beginning, activated astrocytes t
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