Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice

• Published in: PloS one 2017-01, Vol.12 (1), p.e0171048-e0171048
• Main Authors: Porte, Baptiste, Chatelain, Clémence, Hardouin, Julie, Derambure, Céline, Zerdoumi, Yasmine, Hauchecorne, Michèle, Dupré, Nicolas, Bekri, Soumeya, Gonzalez, Bruno, Marret, Stéphane, Cosette, Pascal, Leroux, Philippe
• Format: Article
• Language: English
• Subjects: Age comparisons; Aging - genetics; Alternative energy sources; Angiogenesis; Animals; Animals, Newborn; Antioxidants; Biochemistry, Molecular Biology; Biology and Life Sciences; Bleeding; Brain; Brain - blood supply; Brain research; Coding; Defects; Development Biology; DNA microarrays; Embryology and Organogenesis; Encephalopathy; Energy; Energy demand; Energy metabolism; Energy Metabolism - genetics; Enrichment; Extracellular matrix; Forebrain; Gene expression; Gene Expression Profiling - methods; Gene Expression Regulation; Gene Ontology; Genes; Genetic aspects; Genomics; Gestation; Glucose; Glycolysis; Health aspects; Hemorrhage; Hybridization; Infants; Integrins; Ischemia; Life Sciences; Mass spectrometry; Mass spectroscopy; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Microvessels - metabolism; Mitochondria; Neonates; Neural coding; Newborn babies; Pathways; Pediatrics; Phosphorylation; Physiological aspects; Premature infants; Prosencephalon; Protein metabolism; Protein turnover; Proteins; Proteome - metabolism; Proteomics; Proteomics - methods; Ribonucleic acid; RNA; RNA transport; Transcription; Transport
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171048

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.