2025/01/01 by Linh Le, Sophia Eliseeva, Elizabeth Plunk +4 · 1 voice · 2 citations
Immunology and Microbiology · Neuroscience · #Immune cells in cancer #Neuroinflammation and Neurodegeneration Mechanisms #Neurological Disease Mechanisms and Treatments
paper · doi:10.1016/j.celrep.2024.115176
openalex publication_date 2025/01/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
Microglia, the resident macrophages of the brain, are derived from the yolk sac and colonize the brain before the blood-brain barrier forms. Once established, they expand locally and require Colony-stimulating-factor-1 receptor (CSF1R) signaling for their development and maintenance. CSF1R inhibitors have been used extensively to deplete microglia in the healthy and diseased brain. In this study, we demonstrated sex-dependent differences in the microglial response to the CSF1R inhibitor PLX3397. Male mice exhibited greater microglial depletion compared to females. Transcriptomic and flow cytometry analysis revealed sex-specific differences in the remaining microglia population, with female microglia upregulating autophagy and proteostasis pathways while male microglia increased mitobiogenesis. Furthermore, manipulating key microglial receptors by using different transgenic mouse lines resulted in changes in depletion efficacies that were also sex dependent. These findings suggest sex-dependent microglial survival mechanisms, which might contribute to the well-documented sex differences in various neurological disorders.