Cell . . . The IL-33 mediated glial cell phagocytosis of neurons promotes synaptic remodeling.

!---- Brain synaptic remodeling occurs throughout life, and regions, including the hippocampus, undergo empirical synaptic remodeling, which is critical to learning and memory consolidation.understanding the influencefactors of synaptic remodeling in neural loops is critical to understanding how experience stabilizes coding in the brain.and among the various influencing factors, the role of the inherent immune system in regulating synaptic formation is constantly evident.small glial cells are the most widely distributed immune cells in the brain.research reports found that small gels are involved in synaptic remodeling.small glial cells come into contact with the dendritic ratchet and devour synaptic components early in the development of the hypothalamus and in the hippocampus.small glial cells can also rely on experience to promote synaptic small ratchet formation.February 7, 2020, the Guyan Researcher Stakes Of Zhejiang University School of Medicine and Wang Lang Associate Researchers team for the first time found that small glial cells used for immunity cause memory forgetting by removing synapses, and further discovered that the complement signaling pathway is involved in the obnoxious forgetting of small glial cells and relies on the activity of memory imprintcells (The immune cells revealed in the brain by The Science.however, the mechanism by which synapses mediated by interactions between neurons and small glial cells re-establish stability changes are not clear. The study of the molecular mechanism ofsmall glial cells to regulate synaptic changes is still in its infancy.recently, the Anna V. Molofsky team from UCSF published an article on Cell entitled Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plastic.the study found that adult hippocampus neurons expressIL-33 in an empirically dependent manner, acting on IL-33 receptors on small glial cells and promoting the swallowing of damaged extracellular matrix (Extracellular Matrix ECM).a study published in Science in 2018 by the team showed that IL-33 regulates the activity and function of small glial cells.study found that IL-33 expression of astrocytes in the thysukal brain and spinal cord promotes small glial cells to eat synapses and limits the number of synapses.team first explored the expression of IL-33 in the brains of adult mice.using Il33mCherry/plus to report gene mice, the authors found that, unlike the developing brain, the majority of neurons in the adult mice that express IL-33 in the brain were neurons in the hippocampus.IL-33 has two subtypes IL-33a and IL-33b, which are regulated by different initiation subs.the authors found that neurons mainly express IL-33b and astrocytes produce IL-33a.using conditional knockout tool neuron-specific Syn1Cre to knock out the expression of IL-33 in neurons, and the il-33 immunostaining authors verified the more detailed distribution of IL-33 expression neurons, with the most abundant tooth-like back region.the authors then used three-month-old reported gene mice to be bred in enriched environment (EE) and social (SI) environments for four weeks, respectively, and found that SI environments reduced IL-33 expression in hippocampus neurons, where EE increased IL-33 expression.the authors observed heterogeneity in the expression of IL-33 in toothed back neurons, and the authors analyzed the correlation between heterogeneity and function of hippocampus neurons using single-core RNA sequencing (single-nucleus RNAing).the authors found that toothed back neurons were divided into two subclasses.used the flow to select Il33mCherry/plus neurons, and the analysis found overlap with one of the subtypes, which are associated with cell adhesion, synaptic assembly, and plasticgene enrichment.the authors found that 18 genes associated with the assembly and remodeling of extracellular matrix esage are also enriched in these neurons.summary, synaptic formation in neurons expressed by IL-33 and ECM reshaping related gene enrichment. Further analysisfound that the level of IL-33 was positively correlated with the density of dendritic ratchets.in order to identify the target cells of IL-33, the authors quantified IL1RL1 (also known as ST2, IL-33 receptors), and found that small and medium glial cells in the hippocampus were the main expression cells, and the flow-sorting qPCR and quantitative in situ hybridization confirmed these results. The absence of IL-33 and small glial cells inneurons leads to a decrease in dendritic ratchet density.using whole-cell diaphragm pliers analysis, it was found that the current frequency decreased after excitable synapses in mice with IL-33 cKO, consistent with the decrease in dendritic ratchet density.the use of a slow virus to deliver IL-33 back to the teeth is also sufficient to facilitate the formation of dendritic ratchets. the integration oftooth-like reborn neurons requires reshaping neural circuits and increasing in the EE environment.the authors explored the role of IL-33 in this process and found that there was no significant change in the number of neurons in il-33 cKO mice, but there was no significant change in the number of neurons in EE for five weeks, with significantly significant reduction in new neurons, decreased dendritic density, and impaired synapse integration compared to the control group.this suggests that the increased empirical dependence of newborn neurons requires the source of the neuronil-33. natural lying the authors then examined whether IL-33 was involved in the memory loop regulation that the hippocampus relied on. the authors found that mice with IL-33 cKO had complete memory arousal and situational resolution. but between 14 and 28 days, cKO mice gradually decreased their situational resolution compared to the control group. this suggests that IL-33, a neuronal source, can improve the accuracy of the hippocampus memory at a long point in time. the authors later found decreased IL-33 expression in the hippocampus in older mice, decreased memory accuracy and synaptic echidna plasticity. Increased release of IL-33 in neurons can improve the structure and function of aging-related improvements in the brain. in order to find the relevant mechanism, the author analyzed the transcriptional spectrum characteristics of small glial cells of the hippocampus after il-33 treatment four hours later. IL-33 treatment, the IL-1 beta, TNF, and a variety of chemofactors of small glial cells were activated. in the upward genes, the A-class scavenger receptor Marco and the connecting protein Gas7 (which is necessary for macrophage phagocytosis) rose significantly. these are consistent with il-33's role in promoting small glial cells. analysis found that after IL-33 treatment, the difference expression of 76 genes associated with ECM, a variety of ECM protease increase significantly, of which Adamts4 and Mmp14 encoded membrane-positioned metalproteinase, mainly used for the crackling of sulmate sulfate proteaprotein polysaccharides (chondroitin sulfateproteoglycans CSPGs), which is the main component of the brain of EECM protein. Aggrecan is a csustocpoint around neurons, with a distinct distribution in the toothed back. immunostaining found that Aggrecan is located in small glial cells CD68 plus lysozyme. the number of CD68 plus lysosomes in small glial cells in IL-33cKO mice decreased, and Aggrecan swallowing decreased by 54%. observed in the body il-33 deficiency can lead to the accumulation of ECM around synapses and a decrease in the density of dendritic ratchets. show that il-33-acting small glial cells are important regulatory cells for ECM removal and synaptic remodeling. the study defines the cell mechanism of IL-33-mediated small glial cells that promote stable synaptic remodeling, and demonstrates that the neuron-derived IL-33-driven small glial cells devour the ECM, leading to increased synaptic plasticity. the removal of ECM and the addition of exogenous IL-33 found in the Alzheimer's disease model contribute to disease treatment, and it also suggests that the molecular mechanisms that regulate the synaptic function of small glial cells in the brain can help develop new strategies for cognitive repair. there are several questions to be answered: more detailed study of the expression properties of IL-33 at the individual neuron level, and the molecular mechanisms of il-33 neuronrelease; .