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Regulation of Microglial Polarization through the NF-kB Pathway by activating Rho/ROCK Pathway induced by LPS Priming in the 5xFAD Mouse Model of AD
- 1 Graduate school, Hebei Medical University, Shijiazhuang, China
- 2 College of Biological Sciences, University of California, Davis; Davis, United States
* Author to whom correspondence should be addressed.
Abstract
The symptoms of Alzheimer's disease (AD) are the deposition of beta-amyloid plaques and chronic neuroinflammation caused by microglia. Its pathological process is closely related to microglia. Microglia have innated immune memory (IIM) and have different roles that vary with animal models of neurodegenerative diseases such as AD. However, how IIM-mediated microglia function is well validated in the 5*FAD model. We want to know if lipopolysaccharide (LPS)-induced IIM in the preclinical period of AD alters microglia polarization. We did this by injecting LPS into 5*FAD mice at 6 weeks (before plaque formation). After 140 days, we assessed microglia polarization and activation of the Rho/ROCK pathway and NF-κB pathway in 5*FAD-initiated and non-initiated mice. Furthermore, the activation of them in microglia was also evaluated. ROCK2 was overexpressed in primary microglia by lentivirus transfection. Then, ROCK2 overexpression model was constructed by CRISPR/Cas9 based on 5*FAD mice. Cross with Tmem119-CreERT2 mice to obtain microglia overexpressing ROCK2 mice. The activation of microglia, and these two pathways were evaluated after LPS-induced IIM. Our expected result is that LPS-induced IIM changes microglial polarization from M1 to M2 by the inhibition of them. The paper only provides theoretical experiment design and possible results about alterations in microglia polarization and their mechanisms after LPS priming stimulates innate immune memory, which needs further research in its mechanisms. Suggestions for more long-term effects and potential therapeutic applications in humans also has been listed for reference
Keywords
Alzheimer’s disease, LPS, Priming, innate immune memory, microglial, polarization, Rho/ROCk pathway, NF-κB pathway
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Cite this article
Xu,Y.;You,K. (2025). Regulation of Microglial Polarization through the NF-kB Pathway by activating Rho/ROCK Pathway induced by LPS Priming in the 5xFAD Mouse Model of AD. Theoretical and Natural Science,73,228-241.
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