RT info:eu-repo/semantics/article
T1 Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems
A1 Bajo Grañeras, Raquel
A1 Ganfornina Álvarez, María Dolores
A1 Martín Tejedor, Esperanza
A1 Sánchez Romero, Diego
K1 Sistema nervioso central - Enfermedades
AB The study of glial derived factors induced by injury anddegeneration is important to understand the nervous systemresponse to deteriorating conditions. We focus on ApolipoproteinD (ApoD), a Lipocalin expressed by glia andstrongly induced upon aging, injury or neurodegeneration.Here we study ApoD function in the brain of wild type andApoD-KO mice by combining in vivo experiments withastrocyte cultures. Locomotor performance, dopamine concentration,and gene expression levels in the substantianigra were assayed in mice treated with paraquat (PQ). Theregulation of ApoD transcription, a molecular screening ofoxidative stress (OS)-related genes, cell viability and oxidationstatus, and the effects of adding human ApoD weretested in astrocyte cultures. We demonstrate that (1) ApoDis required for an adequate locomotor performance, modifiesthe gene expression profile of PQ-challenged nigrostriatalsystem, and contributes to its functional maintenance; (2)ApoD expression in astrocytes is controlled by the OSresponsiveJNK pathway; (3) ApoD contributes to anautocrine protecting mechanism in astrocytes, avoiding peroxidatedlipids accumulation and altering the PQ transcriptionalresponse of genes involved in ROS managing and theinflammatory response to OS; (4) Addition of human ApoDto ApoD-KO astrocytes promotes survival through a mechanismaccompanied by protein internalization and modulationof astroglial reactivity. Our data support that ApoDcontributes to the endurance of astrocytes and decreasestheir reactivity level in vitro and in vivo. ApoD function asa maintenance factor for astrocytes would suffice to explainthe observed protection by ApoD of OS-vulnerable dopaminergiccircuits in vivo.
PB Wiley-Liss
SN 0894-1491
YR 2011
FD 2011
LK http://uvadoc.uva.es/handle/10324/6085
UL http://uvadoc.uva.es/handle/10324/6085
LA eng
NO Glia, 2011, vol. 59, p. 1551-1566
NO Producción Científica
DS UVaDOC
RD 27-abr-2024