RT info:eu-repo/semantics/article
T1 Dual role of Apolipoprotein D as long-term instructive factor and acute signal conditioning microglial secretory and phagocytic responses
A1 Corraliza Gómez, Miriam
A1 Bendito Guilarte, Beatriz
A1 Sandonis Camarero, David
A1 Mondéjar Duran, Jorge
A1 Villa, Miguel
A1 Poncela, Marta
A1 Valero Gómez Lobo, Jorge
A1 Sánchez Romero, Diego
A1 Ganfornina Álvarez, María Dolores
K1 Neurobiología
K1 Bioquímica
K1 Citología
K1 Inmunología
K1 microglía
K1 secreción de citocinas
K1 fagocitosis de mielina
K1 endocitosis de beta-amiloide
K1 proteína de unión a membrana
K1 memoria inmunitaria
K1 respuesta aguda
K1 interacción entre astrocitos y microglías
K1 2403 Bioquímica
K1 2407.04 Citología
K1 2412 Inmunología
AB Microglial cells are recognized as very dynamic brain cells, screening the environment and sensitive to signals from all other cell types in health and disease. Apolipoprotein D (ApoD), a lipid-binding protein of the Lipocalin family, is required for nervous system optimal function and proper development and maintenance of key neural structures. ApoD has a cell and state-dependent expression in the healthy nervous system, and increases its expression upon aging, damage or neurodegeneration. An extensive overlap exists between processes where ApoD is involved and those where microglia have an active role. However, no study has analyzed the role of ApoD in microglial responses. In this work, we test the hypothesis that ApoD, as an extracellular signal, participates in the intercellular crosstalk sensed by microglia and impacts their responses upon physiological aging or damaging conditions. We find that a significant proportion of ApoD-dependent aging transcriptome are microglia-specific genes, and show that lack of ApoD in vivo dysregulates microglial density in mouse hippocampus in an age-dependent manner. Murine BV2 and primary microglia do not express ApoD, but it can be internalized and targeted to lysosomes, where unlike other cell types it is transiently present. Cytokine secretion profiles and myelin phagocytosis reveal that ApoD has both long-term pre-conditioning effects on microglia as well as acute effects on these microglial immune functions, without significant modification of cell survival. ApoD-triggered cytokine signatures are stimuli (paraquat vs. Aβ oligomers) and sex-dependent. Acute exposure to ApoD induces microglia to switch from their resting state to a secretory and less phagocytic phenotype, while long-term absence of ApoD leads to attenuated cytokine induction and increased myelin uptake, supporting a role for ApoD as priming or immune training factor. This knowledge should help to advance our understanding of the complex responses of microglia during aging and neurodegeneration, where signals received along our lifespan are combined with damage-triggered acute signals, conditioning both beneficial roles and limitations of microglial functions.
PB Frontiers
SN 1662-5102
YR 2023
FD 2023
LK https://uvadoc.uva.es/handle/10324/82937
UL https://uvadoc.uva.es/handle/10324/82937
LA eng
NO Frontiers in Cellular Neuroscience, 2023, vol. 17, p. 1-14.
NO Producción Científica
DS UVaDOC
RD 21-feb-2026