RT Journal Article
T1 Long-term reprogramming of primed microglia after moderate inhibition of CSF1R signaling.
A1 León-Rodríguez, Ana
A1 Mateos-Grondona, Jesús
A1 Marín Wong, Sonia
A1 López-Aranda, Manuel Francisco
A1 López-Ávalos, María  Dolores
K1 Microglia - Investigación
K1 Sistema nervioso - Enfermedades
AB In acute neuroinflammation, microglia activate transiently, and return to a resting state later on. However, they may retain immune memory of such event, namely priming. Primed microglia are more sensitive to new stimuli and develop exacerbatedresponses, representing a risk factor for neurological disorders with an inflammatory component. Strategies to control the hyperactivation of microglia are, hence, of great interest. The receptor for colony stimulating factor 1 (CSF1R),expressed in myeloid cells, is essential for microglia viability, so its blockade with specific inhibitors (e.g. PLX5622) results in significant depletion of microglial population. Interestingly, upon inhibitor withdrawal, new naïve microglia repopulate thebrain. Depletion-repopulation has been proposed as a strategy to reprogram microglia. However, substantial elimination of microglia is inadvisable in human therapy. To overcome such drawback, we aimed to reprogram long-term primed microgliaby CSF1R partial inhibition. Microglial priming was induced in mice by acute neuroinflammation, provoked by intracerebroventricular injection of neuraminidase. After 3-weeks recovery, low-dose PLX5622 treatment was administrated for12 days, followed by a withdrawal period of 7 weeks. Twelve hours before euthanasia, mice received a peripheral lipopolysaccharide (LPS) immune challenge, and the subsequent microglial inflammatory response was evaluated. PLX5622 provoked a 40%–50% decrease in microglial population, but basal levels were restored 7 weeks later. In the brain regions studied, hippocampus and hypothalamus, LPS induced enhanced microgliosis and inflammatory activation in neuraminidaseinjected mice, while PLX5622 treatment prevented these changes. Our results suggest that PLX5622 used at low doses reverts microglial priming and, remarkably, prevents broad microglial depletion.
PB Wiley
YR 2024
FD 2024
LK https://hdl.handle.net/10630/35255
UL https://hdl.handle.net/10630/35255
LA eng
NO León-Rodríguez, A., Grondona, J. M., Marín-Wong, S., López-Aranda, M. F., & López-Ávalos, M. D. (2024). Long-term reprogramming of primed microglia after moderate inhibition of CSF1R signaling. Glia, 1–21. https://doi.org/10.1002/glia.24627
NO Ministerio de Economía, Industria y Competitividad, Grant/Award Number: SAF2017-83645; Ministerio de Ciencia, Innovación y Universidades, Grant/Award Number: PID2022-141741NB-I00
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 24 ene 2026