title: Amyloid β peptide-mediated neurotoxicity is attenuated by the proliferating microglia more potently than by the quiescent phenotype.
abstract: BACKGROUND
  The specific role of microglia on Aβ-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 Aβ-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 β (Aβ), and the beneficial or destructive effects on neurons were investigated. DPM may induce both direct neurotoxicity without exogenous stimulation and indirect neurotoxicity after Aβ activation. On the other hand, PAM attenuates Aβ-mediated neurotoxicity through Aβ phagocytosis and/or Aβ degradation.
  
  
  CONCLUSIONS
  Our results suggest that the proliferating microglia, but not the differentiated microglia, protect neurons against Aβ-mediated neurotoxicity. This discovery may be helpful on the therapeutic investigation of Alzheimer's disease.
authors.forename: Huey-Jen
authors.initials: HJ
authors.lastname: Tsay
authors.forename: Yung-Cheng
authors.initials: YC
authors.lastname: Huang
authors.forename: Fong-Lee
authors.initials: FL
authors.lastname: Huang
authors.forename: Chia-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Tsai
authors.forename: Ying-Hsiu
authors.initials: YH
authors.lastname: Wang
authors.forename: Mine-Fong
authors.initials: MF
authors.lastname: Wu
authors.forename: Feng-Yi
authors.initials: FY
authors.lastname: Chiang
authors.affiliation: Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei 11221, Taiwan. yshiao@nricm.edu.tw.
authors.forename: Young-Ji
authors.initials: YJ
authors.lastname: Shiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides