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Role of Astrocytes in Manganese Neurotoxicity Revisited
Tao Ke1, Marta Sidoryk-Wegrzynowicz2, Edward Pajarillo3
1Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
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.
Insights
Manganese overexposure causes neurotoxicity, mimicking Parkinson's disease. Astrocytes play a key role in this damage through neurotransmitter imbalance and neuroinflammation, with genetics also contributing to manganese toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Cell Biology
Background:
- Manganese (Mn) overexposure is a significant public health issue due to industrial use and environmental contamination.
- Mn neurotoxicity, or manganism, shares pathological features with Parkinson's disease (PD).
- Astrocytes are brain cells that preferentially accumulate manganese.
Purpose of the Study:
- To review the role of astrocytes in manganese-induced neurotoxicity.
- To explore mechanisms including neurotransmitter recycling, neuroinflammation, and genetic factors.
Main Methods:
- Literature review focusing on astrocytic function in Mn neurotoxicity.
- Analysis of studies on neurotransmitter cycling (glutamine/glutamate).
- Examination of research on neuroinflammation and genetic associations with Mn toxicity.
Main Results:
- Mn overexposure disrupts astrocytic cycling of glutamine and glutamate, leading to excitotoxic neuronal injury.
- Reactive astrocytes contribute to neuronal damage by exacerbating neuroinflammation.
- Genetic studies have identified genes associated with Mn neurotoxicity, including in model organisms like C. elegans.
Conclusions:
- Astrocytes are central players in Mn-induced neurotoxicity and neurodegeneration.
- Understanding astrocytic roles in neurotransmitter regulation and neuroinflammation is crucial for addressing manganism.
- Further research is needed to fully elucidate astrocyte involvement in manganism's pathology.
