Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Reagents
2.3. Mesencephalic Neuron-Glia Culture
2.4. Primary Cortical Mixed Glial Culture
2.5. Microglia-Enriched Cultures
2.6. RNA Analysis
2.7. Dopamine Uptake Assay
2.8. Immunocytochemical and Immunofluorescence Staining
2.9. Western Blot Analysis
2.10. Statistics
3. Results
3.1. MAC1-Deficiency Reduces LPS-Induced Chronic but Not Acute Brain Inflammation
3.2. LPS-Elicited Loss of Dopaminergic Neurons Was Ameliorated in MAC1-Deficient Mouse Brains
3.3. Reactive Microgliosis Was Reduced in LPS-Treated MAC1- or NOX2-Deficient Neuron/Glia Cultures
3.4. Persistent Elevation of Brain Oxidative Stress Was Ameliorated in MAC1 KO Mice
3.5. LPS-Elicited p47phox Translocation Was Reduced in MAC1 KO Microglia
3.6. Prolonged Increase ERK1/2 Phosphorylation Is Associated with MAC1-NOX2 Elicited Reactive Microgliosis
3.7. Inhibition of Activation of ERK1/2 Protects Dopaminergic Neurons from LPS-Elicited Toxicity
4. Discussion
4.1. TLR-4 vs. MAC1
4.2. Role of the MAC-1-NOX2-ERK1/2 Signaling Pathway in LPS-Elicited Chronic Neuroinflammation
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Chen, S.-H.; Han, S.; Hu, C.-F.; Zhou, R.; Gao, Y.; Tu, D.; Gao, H.; Feng, J.; Wang, Y.; Lu, R.-B.; et al. Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration. Antioxidants 2022, 11, 1202. https://doi.org/10.3390/antiox11061202
Chen S-H, Han S, Hu C-F, Zhou R, Gao Y, Tu D, Gao H, Feng J, Wang Y, Lu R-B, et al. Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration. Antioxidants. 2022; 11(6):1202. https://doi.org/10.3390/antiox11061202
Chicago/Turabian StyleChen, Shih-Heng, Shuangyu Han, Chih-Fen Hu, Ran Zhou, Yun Gao, Dezhen Tu, Huiming Gao, Jing Feng, Yubao Wang, Ru-Band Lu, and et al. 2022. "Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration" Antioxidants 11, no. 6: 1202. https://doi.org/10.3390/antiox11061202
APA StyleChen, S.-H., Han, S., Hu, C.-F., Zhou, R., Gao, Y., Tu, D., Gao, H., Feng, J., Wang, Y., Lu, R.-B., & Hong, J.-S. (2022). Activation of the MAC1-ERK1/2-NOX2 Pathway Is Required for LPS-Induced Sustaining Reactive Microgliosis, Chronic Neuroinflammation and Neurodegeneration. Antioxidants, 11(6), 1202. https://doi.org/10.3390/antiox11061202