RT Conference Proceedings
T1 Partial inhibition of CSF1R signaling reverses long-term microglial priming.
A1 León-Rodríguez, Ana
A1 Mateos-Grondona, Jesús
A1 Marín Wong, Sonia
A1 López-Ávalos, María  Dolores
K1 Cerebro - Investigación
K1 Cerebro - Inflamación - Tratamiento
AB Microglial cells are main actors in acute neuroinflammation, during which they activate to laterreturn to a basal resting state. Sometimes they retain immune memory of previousneuroinflammatory events, turning into primed microglia, which develop exacerbated responsesto new stimuli. Brain can be depleted of microglia by treatment with the CSF1R inhibitor PLX5622.Treatment termination allows for microglia regeneration, new cells presenting a resting state. Here we aimed to explore if treatment with lower doses of PLX5622 can reverse microglial priming. We inducedmicroglial priming in mice by provoking acute neuroinflammation by icvadministration of neuraminidase. After 3 weeks, when neuroinflammation is largely solved, micewere treated with a daily dose of PLX5622 for 12 days. Then, microglial repopulation was allowedfor 7 weeks. Finally, a second stimulus was applied (ip LPS) to induce inflammatoryactivation of primed microglia, and animals were sacrificed 12 hours later. Brains were collectedto analyze microglial cell number and activation by morphological analysis, and expression levelof key genes by qPCR; these parameters were evaluated in two regions: the periventricular area ofthe hypothalamus and the hippocampus. In hypothalamic paraventricular nucleus the number ofmicroglial cells was the same regardless the treatment; however, it was slightly reduced in thedentate gyrus of the hippocampus of PLX5622 treated mice. Morphological analysis of microglialcells was carried out by fractal, sholl and skeleton analysis. All of them pointed that microgliasampled from NA injected mice had a more activated profile (less ramified cells), which wasreversed by PLX5622 treatment. Besides, expression of pro-inflammatory related genes (IL1β,IL6, TNFα, NLRP3, TLR4) pointed to the same direction. Thus, our results suggest that PLX5622used at low doses reverses microglial priming, while does not fully deplete microglial population.
YR 2023
FD 2023
LK https://hdl.handle.net/10630/27674
UL https://hdl.handle.net/10630/27674
LA eng
NO Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech.
DS RIUMA. Repositorio Institucional de la Universidad de Málaga
RD 19 ene 2026