To Kill a Microglia: A Case for CSF1R Inhibitors

Abstract

Microglia, the brain's immune sentinels, have garnered much attention in recent years. Researchers have begun to identify the manifold roles that these cells play in the central nervous system (CNS), and this work has been greatly facilitated by microglial depletion paradigms. The varying degrees of spatiotemporal manipulation afforded by such techniques allow microglial ablation before, during, and/or following insult, injury, or disease. We review the major methods of microglial depletion, including toxin-based, genetic, and pharmacological approaches, which differ in key factors including depletion onset, duration, and off-target effects. We conclude that pharmacological CSF1R inhibitors afford the most extensive versatility in manipulating microglia, making them ideal candidates for future studies investigating microglial function in health and disease.

Figure 1.

Widespread Depletion of Murine Microglia with Orally Administered Colony-Stimulating Factor 1 Receptor (CSF1R) Inhibitors. For illustrative purposes, wild-type mice aged 2 months were treated with the CSF1R inhibitor PLX3397 (600 ppm in chow) for 1, 2, or 7 days. Controls were treated for 7 days with vehicle chow. To visualize microglial depletion, representative micrographs of brain sections stained via chromogenic immunohistochemistry using the common microglial marker ionized calcium binding adaptor molecule 1 (IBA1) are shown. Higher-resolution images are provided as insets. Scale bar, 120 μm.