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oai:uvadoc.uva.es:10324/60852021-06-23T09:51:38Zcom_10324_1134com_10324_931com_10324_894col_10324_1213

2015-09-19T23:40:08Z urn:hdl:10324/6085 Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems Bajo Grañeras, Raquel Ganfornina Álvarez, María Dolores Martín Tejedor, Esperanza Sánchez Romero, Diego Sistema nervioso central - Enfermedades Producción Científica The study of glial derived factors induced by injury and degeneration is important to understand the nervous system response to deteriorating conditions. We focus on Apolipoprotein D (ApoD), a Lipocalin expressed by glia and strongly induced upon aging, injury or neurodegeneration. Here we study ApoD function in the brain of wild type and ApoD-KO mice by combining in vivo experiments with astrocyte cultures. Locomotor performance, dopamine concentration, and gene expression levels in the substantia nigra were assayed in mice treated with paraquat (PQ). The regulation of ApoD transcription, a molecular screening of oxidative stress (OS)-related genes, cell viability and oxidation status, and the effects of adding human ApoD were tested in astrocyte cultures. We demonstrate that (1) ApoD is required for an adequate locomotor performance, modifies the gene expression profile of PQ-challenged nigrostriatal system, and contributes to its functional maintenance; (2) ApoD expression in astrocytes is controlled by the OSresponsive JNK pathway; (3) ApoD contributes to an autocrine protecting mechanism in astrocytes, avoiding peroxidated lipids accumulation and altering the PQ transcriptional response of genes involved in ROS managing and the inflammatory response to OS; (4) Addition of human ApoD to ApoD-KO astrocytes promotes survival through a mechanism accompanied by protein internalization and modulation of astroglial reactivity. Our data support that ApoD contributes to the endurance of astrocytes and decreases their reactivity level in vitro and in vivo. ApoD function as a maintenance factor for astrocytes would suffice to explain the observed protection by ApoD of OS-vulnerable dopaminergic circuits in vivo. 2014-09-19T11:17:47Z 2015-09-19T23:40:08Z 2011 info:eu-repo/semantics/article Glia, 2011, vol. 59, p. 1551-1566 0894-1491 http://uvadoc.uva.es/handle/10324/6085 10.1002/glia.21200 1551 1566 Glia 59 eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/4.0/ Attribution-NonCommercial-NoDerivatives 4.0 International Wiley-Liss