Effects of Microglial Cathepsin Z deficiency on postnatal brain development and aging

Title: Effects of Microglial Cathepsin Z Deficiency on Postnatal Brain Development and Aging Aim: Microglial cells secrete numerous cathepsins with various functions along with the immune response. Microglial cathepsins can be located intracellularly and extracellularly and are produced as inactive precursors. Cathepsin Z, a lysosomal cysteine protease, is highly expressed by microglia. This study aims to investigate the effect of microglial Cathepsin Z deficiency on microglial cells and C1q in the postnatal period (P16) and in aging brain .Additionally, the impact of microglial cathepsin Z deficiency on memory in aged mice was examined with Barnes Maze test. Methods: Cathepsin Z (CtsZ) was knocked out (cKO) in microglial cells expressing Cx3Cr1 in an inducible manner by tamoxifen (TAM), generating mice carrying a Cre-conditional ("floxed") allele of our target gene. Immunohistochemistry was performed to detect Microglia (IBA1) and C1q. Brain cell density analysis was performed using toluidine blue staining. The effects of microglial cathepsin Z deficiency on spatial learning and memory were assessed using the Barnes maze test. Results: It was found that microglial cathepsin Z deficiency statistically significantly affected the morphology of microglia in both groups. There was no statistically significant effect observed on the density profile of microglia, nor on C1q immunoreactivity. The Barnes maze test results indicated short-term memory impairments in mice deficient in microglial cathepsin Z. Conclusion: Microglial cathepsin Z deficiency was found to have a certain level of impact on the brain during both early postnatal stages and aging brain. This research, being the first to examine the effects of a protease deficiency on microglial cells, the complement system, and spatial learning and memory, can serve as a foundation for future study.