Abstract
Previous studies reported that astrocyte response to amyloid-β (Aβ) before obvious neuronal damage could be detected in Alzheimer’s disease (AD). It is suggested that astrocytes play a key role in AD pathologies. In this study, we investigated the effects of Aβ42 oligomer on the proliferation and activation of astrocytes by in vitro experiments. The results showed that Aβ42 oligomers could convert astrocytes to responsive astrocytes. It was revealed by MTT and ELISA assays that the viability of astrocytes gradually decreased, and the release of brain-derived neurotrophic factor increased with elevated Aβ42 concentration and prolonged duration. Reverse-transcription polymerase chain reaction (RT-PCR) assay indicated that Aβ42 oligomers increased the expression of glial fibers acid protein and interleukin-1β in a dose-dependent but not time-dependent manner. It was showed that A8, a mouse monoclonal antibody, was able to protect the cultured astrocytes against the toxicity of Aβ42 oligomers. The result demonstrated that A8 could inhibit Aβ42 oligomers toxic effects on astrocytes and that, alone, A8 could promote the proliferation of astrocytes in certain time. The present study laid a theoretical foundation for further understanding the effects of Aβ42 on astrocytes and, hence, is conducive to the theoretical understanding and clinical therapies of AD progression.
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Acknowledgments
This work was supported by National Infrastructure of Natural Science and Technology Program (2005DKA21101) and Key Projects in the National Science and Technology Pillar Program during the Eleventh Five-Year Plan Period (2008BAK41B01-5), and the Ministry of Agriculture of China for Transgenic Research Program (2008ZX08009-003). The authors thank Mr. Dapeng Jin for critical reading of the manuscript.
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Editor: T. Okamoto
Lingling Hou and Yanfeng Liu contributed equally to this work.
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Hou, L., Liu, Y., Wang, X. et al. The effects of amyloid-β42 oligomer on the proliferation and activation of astrocytes in vitro. In Vitro Cell.Dev.Biol.-Animal 47, 573–580 (2011). https://doi.org/10.1007/s11626-011-9439-y
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DOI: https://doi.org/10.1007/s11626-011-9439-y