LPS Priming Before Plaque Deposition Activates the Rho/ROCK Pathway to Regulate Microglial M1/M2 Polarization Through the NF-κB Pathway in the 5xFAD Mouse Model of Alzheimer’s Disease

Abstract

Alzheimer’s Disease is a neurodegenerative disease which is characterized by continuous neuroinflammation, beta-amyloid plaques (Aβ) and tau clusters. Microglia is a type of immune cell that resides in the brain and plays a crucial role in disease progression and neuroprotection based on its extent of polarization. This research investigated the effect on microglial polarization caused by LPS priming before plaque deposition through the Rho/ROCK pathway and the NF-κB pathway in a 5xFAD mouse model. It is assumed that LPS priming will activate the Rho/ROCK pathway and then regulate the NF-κB pathway, causing microglial polarization from M1 (pro-inflammatory state) to M2 (inflammatory state). To achieve this goal, the techniques applied include immunohistochemistry, flow cytometry, Western blotting, and RT-qPCR. The expected result is the observation that LPS priming increased Rho/ROCK activation, inhibited the NF-κB pathway, and promoted M2 polarization. This observation indicates the complex relationship between systemic and neuroinflammatory pathways in AD. Moreover, it provides potential therapeutic approaches targeting Rho/ROCK and NF-κB pathways to reduce neuroinflammation and enhance neuroprotection.