Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model
Abstract
:1. Introduction
2. Materials and Methods
2.1. Reagents
2.2. Mice Dosing
2.3. Gait Measurement
2.4. Evans Blue Content
2.5. Immunohistochemistry
2.6. Real-Time PCR
2.7. Western Blot
2.8. Statistical Analysis
3. Results
3.1. Rotenone Increases BBB Permeability
3.2. Rotenone Dose-Dependently Decreases Expression of TJ Proteins in the Substantia Nigra of Mice
3.3. Microglial Activation Mediates BBB Disruption in Rotenone-Lesioned Mice
3.4. Microglial Depletion and Inactivation Attenuate MMP-2/-9 Activation in Rotenone-Treated Mice
3.5. Inhibition of MMP-2/-9 Activation Mitigates Rotenone-Elicited BBB Dysfunction
3.6. Microglial Depletion, Inactivation and Inhibition of MMP2/9 Protect Dopaminergic Neurons in Rotenone-Injected Mice
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer disease |
BBB | blood–brain barrier |
Iba-1 | ionized calcium binding adaptor molecule-1 |
LPS | lipopolysaccharide |
MMP-2/-9 | metalloproteinases 2 and 9 |
PD | Parkinson’s disease |
PFA | paraformaldehyde |
THir | TH-positive |
TJ | tight junction |
TLR4 | toll like receptor-4 |
ZO-1 | zonula occludens-1 |
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Ruan, Z.; Zhang, D.; Huang, R.; Sun, W.; Hou, L.; Zhao, J.; Wang, Q. Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model. Int. J. Mol. Sci. 2022, 23, 2793. https://doi.org/10.3390/ijms23052793
Ruan Z, Zhang D, Huang R, Sun W, Hou L, Zhao J, Wang Q. Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model. International Journal of Molecular Sciences. 2022; 23(5):2793. https://doi.org/10.3390/ijms23052793
Chicago/Turabian StyleRuan, Zhengzheng, Dongdong Zhang, Ruixue Huang, Wei Sun, Liyan Hou, Jie Zhao, and Qingshan Wang. 2022. "Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model" International Journal of Molecular Sciences 23, no. 5: 2793. https://doi.org/10.3390/ijms23052793
APA StyleRuan, Z., Zhang, D., Huang, R., Sun, W., Hou, L., Zhao, J., & Wang, Q. (2022). Microglial Activation Damages Dopaminergic Neurons through MMP-2/-9-Mediated Increase of Blood-Brain Barrier Permeability in a Parkinson’s Disease Mouse Model. International Journal of Molecular Sciences, 23(5), 2793. https://doi.org/10.3390/ijms23052793