title: Apolipoprotein D alters the early transcriptional response to oxidative stress in the adult cerebellum.
abstract: The lipocalin Apolipoprotein D (ApoD), known to protect the nervous system against oxidative stress (OS) in model organisms, is up-regulated early in the mouse brain in response to the ROS generator paraquat. However, the processes triggered by this up-regulation have not been explored. We present here a study of the effect of ApoD on the early transcriptional changes upon OS in the mouse cerebellum using microarray profiling. ApoD-KO and transgenic mice over-expressing ApoD in neurons are compared to wild-type controls. In control conditions, ApoD affects the transcriptional profile of neuron and oligodendrocyte-specific genes involved in neuronal excitability, synaptic function, and myelin homeostasis. When challenged with paraquat, the absence of ApoD modifies the response of genes mainly related to OS management and myelination. Interestingly, the over-expression of ApoD in neurons almost completely abolishes the early transcriptional response to OS. We independently evaluate the expression of protein kinase Cδ, a gene up-regulated by OS only in the ApoD-KO cerebellum, and find it over-expressed in cultured ApoD-KO primary astrocytes, which points to a role for ApoD in astrocyte-microglia signaling. Our results support the hypothesis that ApoD is necessary for a proper response of the nervous system against physiological and pathological OS.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Fisiología-IBGM, Universidad de Valladolid-CSIC, Valladolid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Bajo-Grañeras
authors.forename: Diego
authors.initials: D
authors.lastname: Sanchez
authors.forename: Gabriel
authors.initials: G
authors.lastname: Gutierrez
authors.forename: Constancio
authors.initials: C
authors.lastname: González
authors.forename: Sonia
authors.initials: S
authors.lastname: Do Carmo
authors.forename: Eric
authors.initials: E
authors.lastname: Rassart
authors.forename: Maria D
authors.initials: MD
authors.lastname: Ganfornina
mesh_terms: D000818:Animals; D053399:Apolipoproteins D / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D015870:Gene Expression; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D014158:Transcription, Genetic
chemical_list: D053399:Apolipoproteins D