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Updated: May 27, 2026
Microglia as a Surrogate Biosensor to Determine Nanoparticle Neurotoxicity
Published on: October 25, 2016
Role of glial cells in manganese neurotoxicity
Nikolay M Filipov1, Celia A Dodd
1Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA. filipov@uga.edu
Abstract:
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.
Insights
Excessive manganese (Mn) exposure triggers neuroinflammation by activating microglia and astrocytes. This glial-driven inflammation contributes to neuronal injury and neurodegeneration, highlighting Mn
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Manganese (Mn) is an essential trace element, but excessive exposure can lead to neurotoxicity.
- Glia, including microglia and astrocytes, play crucial roles in brain homeostasis and disease.
- Neuroinflammation is increasingly recognized as a key factor in various neurodegenerative conditions.
Purpose of the Study:
- To systematically review recent advances on the role of glia (microglia and astrocytes) in manganese-induced neuropathology.
- To highlight mechanisms of manganese-modulated, glia-derived neuroinflammation.
- To discuss the implications of this neuroinflammation on neuronal injury following manganese overexposure.
Main Methods:
- Systematic review of existing in vitro and in vivo studies.
- Analysis of literature on glial activation and neuroinflammation in the context of manganese exposure.
- Examination of molecular pathways involved in manganese's effects on glial and neuronal cells.
Main Results:
- Manganese acts as a modulator of glial activation, leading to neuroinflammation.
- Specific mechanisms underlying manganese-induced glial inflammatory responses are identified.
- Manganese-modulated glial activation contributes significantly to neuronal injury.
Conclusions:
- Glia, particularly microglia and astrocytes, are central players in manganese neurotoxicity.
- Understanding manganese-modulated neuroinflammation is critical for addressing manganese-induced neurodegeneration.
- Further research is needed to fill existing data gaps regarding manganese and glial-mediated neuroinflammation.
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