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Survival factors for human microglia

ABSTRACT: Microglia is a type of neuroglia (glial cell) located in entire brain and spinal cord playing a crucial role in microglial-associated disorders, immunity, homeostasis of brain and neuronal recovery. Except few growth factors, no drugs are available to enhance the microglial cell survival. Therefore, identification of factors inducing microglia survival is a cost effectove therapeutic intervention which may be utilized in various microglia associated disorders. Cells were treated with drugs (muscarinic receptor antagonists) that may have a role in cell survival and total RNA was isolated from three idenpendent exprements and pooled for whole-transcriptome sequencing. The gene expression analysis suggested that drugs exhibits microglia survival properties by reducing the caspase activation and other pro-apoptotic factors. In addtion, the anti-apoptotic genes were found to be significanlty upregulated. Furthermore, microglia associated diorders genes were analyzed and was found that the drug may be effective for the treatment of range of neurological disorders.

ORGANISM(S): Homo sapiens

PROVIDER: GSE140534 | GEO | 2025/11/08

REPOSITORIES: GEO

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Project description:Microglia colonize the brain parenchyma at early stages of development and accumulate in specific regions where they actively participate in cell death, angiogenesis, neurogenesis and synapse elimination. A recurring feature of embryonic microglial distribution is their association with developing axon tracts which, together with in vitro data, supports the idea of a physiological role for microglia in neurite development. Yet the demonstration of this role of microglia is still lacking. Here, we have studied the consequences of microglial dysfunction on the formation of the corpus callosum, the largest connective structure in the mammalian brain, which shows consistent microglial accumulation during development. We studied two models of microglial dysfunction: the loss-of-function of DAP12, a key microglial-specific signaling molecule, and a model of maternal inflammation by peritoneal injection of LPS at E15.5. We performed transcriptional profiling of maternally inflamed and Dap12-mutant microglia at E17.5. We found that both treatments principally down-regulated genes involved in nervous system development and function, particularly in neurite formation. We then analyzed the functional consequences of these microglial dysfunctions on the formation of the corpus callosum. We also took advantage of the Pu.1-/- mouse line, which is devoid of microglia. We now show that all three models of altered microglial activity resulted in the same defasciculation phenotype. Our study demonstrates that microglia are actively involved in the fasciculation of corpus callosum axons. To investigate possible roles for microglial during brain development, we challenged microglial function by two complementary approaches. First, we induced maternal inflammation by peritoneal injection of LPS into pregnant dams. Next, we analyzed the consequences of a loss of function of DAP12, a signaling molecule specifically expressed in microglia that is crucial for several aspects of microglia biology (references in Wakselman et al., 2008). We compared the gene expression profiles of microglia from control, maternally-inflamed by LPS (MI), and Dap12-mutated embryos. We isolated RNA from FACS sorted maternally inflamed (by LPS) and Dap12-mutant microglia at E17.5 pooled per pregnant dam; as a control we included PBS treated and untreated (UT) microglia. We compared gene expression between maternally inflamed microlgia (PBSvsLPS) and DAP12-mutant microglia (UTvsDAP12KO).

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Survival factors for human microglia

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