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

Baptiste Porte (1, 2) , Clémence Chatelain (1, 2) , Julie Hardouin (3, 4) , Céline Derambure (1) , Yasmine Zerdoumi (1) , Michèle Hauchecorne (1, 2) , Nicolas Dupré (1, 2) , Soumeya Bekri (5, 1) , Bruno J. Gonzalez (1, 2) , Stéphane Marret (1, 2, 6) , Pascal Cosette (4) , Philippe Leroux (1, 2)

1 GPMCND - Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques
2 Neovasc - Team 4 NeoVasc - Region Team ERI 28 INSERM
3 PBS - Polymères Biopolymères Surfaces
4 Plate-forme de Protéomique PISSARO
5 Laboratoire de biochimie générale [Rouen]
6 Service de Pédiatrie Néonatale et Réanimation – Neuropédiatrie [CHU Rouen]

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 knockout 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 twofold change in expression. Five major biological functions were observed in those genes detected both as proteins and mRNA expression undergoing at least a twofold change in expression in one or more age comparisons: energy metabolism , protein metabolism, antioxidant function, ion exchanges, and transport. Adult micro-vessels 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 glycoly-sis 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.

Domaines: Génomique, Transcriptomique et Protéomique [q-bio.GN]; Embryologie et organogenèse

Baptiste Porte, Clémence Chatelain, Julie Hardouin, Céline Derambure, Yasmine Zerdoumi, et al.. Proteomic and transcriptomic study of brain microvessels in neonatal and adult mice. PLoS ONE, 2017, 12, pp.e0171048. ⟨10.1371/journal.pone.0171048⟩. ⟨hal-02445354⟩