Microarray Analysis Revealed Inflammatory Transcriptomic Changes after LSL60101 Treatment in 5XFAD Mice Model

Abstract

I2-IR have been found dysregulated in patients with neurodegenerative diseases, such as Alzheimer’s disease (AD), in which the importance of neuroinflammation in the establishment and maintenance of cognitive decline is well-documented. To research the implication of I2-IR in neuroinflammatory pathways altered in AD, we determined the expression profile of genes associated with inflammation in the 5XFAD model treated with LSL60101, a well-established I2-IR ligand. Thus, we performed a qPCR array containing 84 inflammation-related genes. Hierarchical clustering analysis revealed three gene clusters, suggesting that treatment with LSL60101 affects the gene expression associated with inflammation in the 5XFAD model. Furthermore, we evaluated the functions of the three clusters; thereby performing a pathway enrichment analysis using the GO database. As we expected, clusters 2 and 3 showed alterations in the inflammatory response, chemotaxis and the chemokine-mediated signaling pathway, among others. To validate previous results from the gene profiling analysis, the expression levels of a representative subset of mRNAs were selected according to the intensity of the observed changes and their biological relevance. Interestingly, changes induced by LSL60101 in the 5XFAD model were validated for several genes. These results suggest that treatment with LSL60101 in the 5XFAD model reverses the inflammatory process during the development of AD.

I2-Imidazoline Ligand CR4056 Improves Memory, Increases ApoE Expression and Reduces BBB Leakage in 5xFAD Mice

“…I2IRs are located mostly in glial cells and we and others have described the antiinflammatory effects of I2-imidazoline ligands. Although there is evidence that I2IR drugs reduce the density of microglia in different models of CNS neuroinflammation [35,37,39] as well as the levels of pro-inflammatory cytokines and ROS [37,44,46,47], no studies have so far investigated the effect of imidazoline ligands on microglia phenotype, including morphological changes. We present now in our study that CR4056 affects also the microglia phagocytic profile, by using the marker CD68.…”