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

Journal of Biomedical Science

Young-Ji Shiao⁵  Feng-Yi Chiang¹  Mine-Fong Wu¹  Ying-Hsiu Wang⁶  Yu-Chun Tsai¹  Chia-Ping Chen¹  Fong-Lee Huang³  Yung-Cheng Huang⁴  Huey-Jen Tsay² 

[1] Institute of Biopharmaceutical Science, National Yang-Ming University, Taipei 11221, Taiwan;Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan;Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei 11221, Taiwan;Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei 11221, Taiwan;Ph.D Program for the Clinical Drug Discovery from Botanical Herbs, College of Pharmacy, Taipei Medical University, Taipei 110, Taiwan, R.O.C;National Research Institute of Chinese Medicine, Taipei 11221, Taiwan, R.O.C

关键词: Neurotoxicity;    Amyloid β protein;    Neuroinflammation;    Functional phenotypes;    Microglia;    Alzheimer’s disease;   

Others  :  821988
DOI  :  10.1186/1423-0127-20-78

 received in 2013-08-07, accepted in 2013-10-20,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Tsay et al.; licensee BioMed Central Ltd.

【 图 表 】

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