Title: Role of Astrocytes in Manganese Neurotoxicity Revisited.
Authors: Ke, Tao; Sidoryk-Wegrzynowicz, Marta; Pajarillo, Edward; Rizor, Asha; Soares, Félix Alexandre Antunes; Lee, Eunsook; Aschner, Michael
Published In Neurochem Res, (2019 Nov)
Abstract: Manganese (Mn) overexposure is a public health concern due to its widespread industrial usage and the risk for environmental contamination. The clinical symptoms of Mn neurotoxicity, or manganism, share several pathological features of Parkinson's disease (PD). Biologically, Mn is an essential trace element, and Mn in the brain is preferentially localized in astrocytes. This review summarizes the role of astrocytes in Mn-induced neurotoxicity, specifically on the role of neurotransmitter recycling, neuroinflammation, and genetics. Mn overexposure can dysregulate astrocytic cycling of glutamine (Gln) and glutamate (Glu), which is the basis for Mn-induced excitotoxic neuronal injury. In addition, reactive astrocytes are important mediators of Mn-induced neuronal damage by potentiating neuroinflammation. Genetic studies, including those with Caenorhabditis elegans (C. elegans) have uncovered several genes associated with Mn neurotoxicity. Though we have yet to fully understand the role of astrocytes in the pathologic changes characteristic of manganism, significant strides have been made over the last two decades in deciphering the role of astrocytes in Mn-induced neurotoxicity and neurodegeneration.
PubMed ID: 31571097
MeSH Terms: Animals; Astrocytes/drug effects; Astrocytes/metabolism*; Brain/metabolism; Cell Line; Glutamic Acid/metabolism; Glutamine/metabolism; Humans; Manganese Poisoning/physiopathology*; Manganese/toxicity*; Neurons/metabolism