Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD
Abstract
:1. Introduction
2. Experimental Procedures
2.1. Ethics Statement
2.2. Cell Culture
2.3. Cell Viability Assay
2.4. mRNA Quantification by RT-PCR
2.5. Real-Time PCR (q-PCR)
2.6. Enzyme-Linked Immunosorbent Assay (ELISA)
2.7. Antibodies and Inhibitors
2.8. Western Blotting
2.9. Immunocytochemistry
2.10. Cytosolic and Nuclear Fractionation
2.11. Primary Microglial Cell and Astrocyte Culture
2.12. Animals
2.13. Immunohistochemistry
2.14. Golgi Staining
2.15. Statistical Analyses
3. Results
3.1. Regorafenib Regulates LPS-Induced Expression of Proinflammatory Cytokines
3.2. Regorafenib Modulates AKT/STAT3 Signaling to Alter LPS-Induced Neuroinflammatory Responses
3.3. Regorafenib Alters LPS-Induced Expression of Proinflammatory Cytokines in Primary Microglia and Astrocytes
3.4. Regorafenib Attenuates LPS-Induced Glial Activation and the Expression of Proinflammatory Cytokines in Wild-Type Mice
3.5. Regorafenib Significantly Increases Dendritic Spine Density in Primary Hippocampal Neurons and in the Brains of 5x FAD Mice
3.6. Regorafenib Significantly Downregulates Aβ Plaque Levels in 5x FAD Mice
3.7. Regorafenib Significantly Reduces Tau Phosphorylation at T212 and S214 and Tau Kinase GSK3β Activity in the Brains of 5x FAD Mice
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Han, K.-M.; Kang, R.J.; Jeon, H.; Lee, H.-j.; Lee, J.-S.; Park, H.; Gak Jeon, S.; Suk, K.; Seo, J.; Hoe, H.-S. Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD. Cells 2020, 9, 1655. https://doi.org/10.3390/cells9071655
Han K-M, Kang RJ, Jeon H, Lee H-j, Lee J-S, Park H, Gak Jeon S, Suk K, Seo J, Hoe H-S. Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD. Cells. 2020; 9(7):1655. https://doi.org/10.3390/cells9071655
Chicago/Turabian StyleHan, Kyung-Min, Ri Jin Kang, Hyongjun Jeon, Hyun-ju Lee, Ji-Soo Lee, HyunHee Park, Seong Gak Jeon, Kyoungho Suk, Jinsoo Seo, and Hyang-Sook Hoe. 2020. "Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD" Cells 9, no. 7: 1655. https://doi.org/10.3390/cells9071655
APA StyleHan, K. -M., Kang, R. J., Jeon, H., Lee, H. -j., Lee, J. -S., Park, H., Gak Jeon, S., Suk, K., Seo, J., & Hoe, H. -S. (2020). Regorafenib Regulates AD Pathology, Neuroinflammation, and Dendritic Spinogenesis in Cells and a Mouse Model of AD. Cells, 9(7), 1655. https://doi.org/10.3390/cells9071655