Role of glial cells in manganese neurotoxicity.

The objectives of this focused review are to (i) provide a systematic overview of recent advances pertaining to the role of glia, namely microglia and astrocytes, in the neuropathology associated with excessive exposure to manganese (Mn), (ii) highlight possible mechanisms and factors involved in Mn-modulated, glia-derived neuroinflammation, and (iii) discuss the implications of excessive neuroinflammation on neuronal injury within the context of Mn overexposure. As this is not meant to be a comprehensive review on the topic of Mn neurotoxicity, the reader may wish to refer to several broader and more comprehensive reviews. After a brief introduction to Mn neurotoxicity, we first discuss the role of glial cells in neurodegeneration. Next, we review existing in vitro and in vivo studies that implicate Mn as a modulator of glial activation and ensuing neuroinflammation. This is followed by an examination of recognized and potential mechanisms that are involved in the modulation of glial inflammatory output by Mn; here the common pathways activated by Mn in glial and neuronal cells, including outcomes of such activation, are also addressed. We finish with a discussion of the implications of Mn-modulated glial activation for neuronal survival and with a list of data gaps in the topic that need to be filled in the future.