Minocycline attenuates A beta oligomers-induced pro-inflammatory phenotype in primary microglia while enhancing A beta fibrils phagocytosis

摘要

Microglia, the brain innate immune cells, are activated in response to amyloid beta (A beta) resulting in neuroinflammation in AD brains. Recently, two phenotypes have been described for microglia: the pro-inflammatory classical and the anti-inflammatory alternative. Changes in microglia phenotype that control their phagocytic function are yet to be determined. The highly neurotoxic A beta oligomers (oA beta) formed at an early disease stage induce pro-inflammatory microglia activation releasing neurotoxic mediators and contributing to neurodegeneration. A novel strategy for AD treatment is to attenuate microglia-induced inflammation while maintaining efficient A beta clearance. Minocycline effectively crosses the blood-brain barrier and has widely reported neuroprotective effects. Yet, its exact mechanism of neuroprotection and its effects on microglia are still unknown. The aim of this study is to investigate the effect of minocycline on the phagocytic uptake of fA beta by primary microglia in relation to their activation state in an inflammatory milieu generated by oA beta or LPS. The study shows that minocycline is able to attenuate oA beta-induced neuroinflammatory response of microglia by inhibiting their pro-inflammatory phenotype activation. In addition, a significant enhancement of fA beta phagocytosis by minocycline- treated microglia is reported for the first time, providing novel insight into its neuroprotective role in AD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.