title: Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice.
abstract: Infants born before 29 weeks gestation incur a major risk of preterm encephalopathy and subependymal/intracerebral/intraventricular haemorrhage. In mice, an ontogenic window of haemorrhage risk was recorded up to 5 days after birth in serpine1 knock-out animals. Using proteome and transcriptome approaches in mouse forebrain microvessels, we previously described the remodelling of extracellular matrix and integrins likely strengthening the vascular wall between postnatal day 5 (P5) and P10. Haemorrhage is the ultimate outcome of vessel damage (i.e., during ischaemia), although discreet vessel insults may be involved in the aetiology of preterm encephalopathy. In this study, we examined proteins identified by mass spectrometry and segregating in gene ontology pathways in forebrain microvessels in P5, P10, and adult wild type mice. In parallel, comparative transcript levels were obtained using RNA hybridization microarrays and enriched biological pathways were extracted from genes exhibiting at least a two-fold change in expression. Five major biological functions were observed in those genes detected both as proteins and mRNA expression undergoing at least a two-fold change in expression in one or more age comparisons: energy metabolism, protein metabolism, antioxidant function, ion exchanges, and transport. Adult microvessels exhibited the highest protein and mRNA expression levels for a majority of genes. Energy metabolism-enriched gene ontology pathways pointed to the preferential occurrence of glycolysis in P5 microvessels cells versus P10 and adult preparations enriched in aerobic oxidative enzymes. Age-dependent levels of RNA coding transport proteins at the plasma membrane and mitochondria strengthened our findings based on protein data. The data suggest that immature microvessels have fewer energy supply alternatives to glycolysis than mature structures. In the context of high energy demand, this constraint might account for vascular damage and maintenance of the high bleeding occurrence in specific areas in immature brain.
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Porte
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Chatelain
authors.affiliation: Normandie Université, UNIROUEN, UMR-6270, CNRS, IRIB, Mont-Saint-Aignan, France.|Normandie Université, UNIROUEN, Proteomic Facility PISSARO, IRIB, Mont-Saint-Aignan, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Hardouin
authors.affiliation: Normandie Université, UNIROUEN, UMR-S905, INSERM, IRIB, Rouen, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Derambure
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Yasmine
authors.initials: Y
authors.lastname: Zerdoumi
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Michèle
authors.initials: M
authors.lastname: Hauchecorne
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dupré
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Metabolic Biochemistry Department, Rouen University Hospital, Rouen, France.
authors.forename: Soumeya
authors.initials: S
authors.lastname: Bekri
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Gonzalez
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.|Neonatal Pediatrics and Intensive Care Department, Rouen University Hospital, Rouen, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Marret
authors.affiliation: Normandie Université, UNIROUEN, UMR-6270, CNRS, IRIB, Mont-Saint-Aignan, France.|Normandie Université, UNIROUEN, Proteomic Facility PISSARO, IRIB, Mont-Saint-Aignan, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Cosette
authors.affiliation: Normandie Université, UNIROUEN, U1245, INSERM, Institute for Research and Innovation in Biomedicine (IRIB), Rouen, France.
authors.forename: Philippe
authors.identifier: http://orcid.org/0000-0002-0183-5427
authors.initials: P
authors.lastname: Leroux
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000098:blood supply*; D004734:Energy Metabolism / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D063990:Gene Ontology; D008810:Mice, Inbred C57BL; D055806:Microvessels / Q000378:metabolism*; D020543:Proteome / Q000378:metabolism; D040901:Proteomics / Q000379:methods*
chemical_list: D020543:Proteome