TY - JOUR
T1 - Role of Astrocytes in Manganese Neurotoxicity Revisited
AU - Ke, Tao
AU - Sidoryk-Wegrzynowicz, Marta
AU - Pajarillo, Edward
AU - Rizor, Asha
AU - Soares, Félix Alexandre Antunes
AU - Lee, Eunsook
AU - Aschner, Michael
N1 - Funding Information:
The present study was supported by National Institute of Environmental Health Sciences in part by R01 ES024756 (EL), R01 ES10563 (MA), 1R03 ES024849 (MA), R01 ES07331 (MA) and 1R21 ES025415 (MA).
Publisher Copyright:
© 2019, Springer Science+Business Media, LLC, part of Springer Nature.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - Astrocyte
KW - Glutamate
KW - Glutamine
KW - Manganese
KW - Neurotoxicity
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U2 - 10.1007/s11064-019-02881-7
DO - 10.1007/s11064-019-02881-7
M3 - Review article
C2 - 31571097
AN - SCOPUS:85073965760
SN - 0364-3190
VL - 44
SP - 2449
EP - 2459
JO - Neurochemical Research
JF - Neurochemical Research
IS - 11
ER -
