- 作者: Huey-Jen Tsay, Yung-Cheng Huang, Fong-Lee Huang, Chia-Ping Chen, Yu-Chun Tsai, Ying-Hsiu Wang, Mine-Fong Wu, Feng-Yi Chiang and Young-Ji Shiao
- 作者服務機構: Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan, R.O.C
- 中文摘要: --
- 英文摘要:
Background: The specific role of microglia on Abeta-mediated neurotoxicity is difficult to assign in vivo due to their complicated environment in the brain. Therefore, most of the current microglia-related studies employed the isolated microglia. However, the previous in vitro studies have suggested either beneficial or destructive function in microglia. Therefore, to investigate the phenotypes of the isolated microglia which exert activity of neuroprotective or destructive is required.
Results: The present study investigates the phenotypes of isolated microglia on protecting neuron against Abeta-mediated neurotoxicity. Primary microglia were isolated from the mixed glia culture, and were further cultured to distinct phenotypes, designated as proliferating amoeboid microglia (PAM) and differentiated process-bearing microglia (DPM). Their inflammatory phenotypes, response to amyloid beta (Abeta), and the beneficial or destructive effects on neurons were investigated. DPM may induce both direct neurotoxicity without exogenous stimulation and indirect neurotoxicity after Abeta activation. On the other hand, PAM attenuates Abeta-mediated neurotoxicity through Abeta phagocytosis and/or Abeta degradation.
Conclusions: Our results suggest that the proliferating microglia, but not the differentiated microglia, protect neurons against Abeta-mediated neurotoxicity. This discovery may be helpful on the therapeutic investigation of Alzheimer's disease. - 中文關鍵字: --
- 英文關鍵字: Alzheimer’s disease, Microglia, Functional phenotypes, Neuroinflammation, Amyloid β protein, Neurotoxicity