Recent advances in neuroscience have revealed that glial cells play a central role in various brain disorders, including neurodegenerative diseases and psychiatric disorders. In particular, microglia play a central role in synaptogenesis and synaptic reorganization/network reorganization by synapse removal, and their abnormalities are closely related to brain diseases. Since colony stimulating factor 1 receptor (CSF1R) signaling is essential for microglial survival, microglia can be removed and replaced by self-renewal by turning on/off an irreversible CSF1R antagonist. Furthermore, the combination of ON/OFF of CSF1R antagonist and microglial nasal transplantation allows for the completely noninvasive transplantation and replacement of endogenous microglia with exogenous ones. In this symposium, we will report the latest findings on the usefulness of microglial replacement as a therapeutic strategy for neurodegenerative diseases, as well as its molecular mechanism, by using an animal model of Alexander's disease. In addition, we will provide an example of completely non-invasive transplantation of human iPS cell-derived microglia into the mouse brain, as well as the latest topics related to the creation of microglial humanized mice and applied research using these mice.