2024-03-29T11:22:38Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/60852021-06-23T09:51:38Zcom_10324_1134com_10324_931com_10324_894col_10324_1213
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.
2015-09-19
2014-09-19T11:17:47Z
2015-09-19T23:40:08Z
2011
info:eu-repo/semantics/article
https://doi.org/10.1002/glia.21200
Glia, 2011, vol. 59, p. 1551-1566
0894-1491
http://uvadoc.uva.es/handle/10324/6085
1551
1566
Glia
59
eng
Attribution-NonCommercial-NoDerivatives 4.0 International
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
Wiley-Liss