Amyloid beta peptide-mediated neurotoxicity is attenuated by the proliferating microglia more potently than by the quiescent phenotype

作者：Tsay Huey Jen; Huang Yung Cheng; Huang Fong Lee; Chen Chia Ping; Tsai Yu Chun; Wang Ying Hsiu; Wu Mine Fong; Chiang Feng Yi; Shiao Young Ji^*

来源：Journal of Biomedical Science, 2013, 20(1): 78.

DOI：10.1186/1423-0127-20-78

• Alzheimer%26apos
• s disease
• Microglia
• Functional phenotypes
• Neuroinflammation
• Amyloid beta protein
• Neurotoxicity

Background: The specific role of microglia on A beta-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. %26lt;br%26gt;Results: The present study investigates the phenotypes of isolated microglia on protecting neuron against A beta-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 (A beta), and the beneficial or destructive effects on neurons were investigated. DPM may induce both direct neurotoxicity without exogenous stimulation and indirect neurotoxicity after A beta activation. On the other hand, PAM attenuates A beta-mediated neurotoxicity through A beta phagocytosis and/or A beta degradation. %26lt;br%26gt;Conclusions: Our results suggest that the proliferating microglia, but not the differentiated microglia, protect neurons against A beta-mediated neurotoxicity. This discovery may be helpful on the therapeutic investigation of Alzheimer%26apos;s disease.

• 出版日期2013-10-23