title: Modeling the neurovascular niche: unbiased transcriptome analysis of the murine subventricular zone in response to hypoxic insult.
abstract: Premature infants often experience chronic hypoxia, resulting in cognitive & motor neurodevelopmental handicaps. These sometimes devastating handicaps are thought to be caused by compromised neural precursor cell (NPC) repair/recovery resulting in variable central nervous system (CNS) repair/recovery. We have identified differential responses of two mouse strains (C57BL/6 & CD1) to chronic hypoxia that span the range of responsiveness noted in the premature human population. We previously correlated several CNS tissue and cellular behaviors with the different behavioral parameters manifested by these two strains. In this report, we use unbiased array technology to interrogate the transcriptome of the subventricular zone (SVZ) in these strains. Our results illustrate differences in mRNA expression in the SVZ of both C57BL/6 and CD1 mice following hypoxia as well as differences between C57BL/6 and CD1 SVZ under both normoxic and hypoxic conditions. Differences in expression were found in gene sets associated with Sox10-mediated neural functions that explain, in part, the differential cognitive and motor responsiveness to hypoxic insult. This may shed additional light on our understanding of the variable responses noted in the human premature infant population and facilitate early intervention approaches. Further interrogation of the differentially expressed gene sets will provide a more complete understanding of the differential responses to, and recovery from, hypoxic insult allowing for more informed modeling of the ranges of disease severity observed in the very premature human population.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Sandra
authors.initials: S
authors.lastname: Canosa
authors.forename: Kelly
authors.initials: K
authors.lastname: Flynn
authors.forename: Michael
authors.initials: M
authors.lastname: Michaud
authors.forename: Michael
authors.initials: M
authors.lastname: Krauthammer
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Madri
mesh_terms: D000818:Animals; D002552:Cerebral Ventricles / Q000098:blood supply* / Q000378:metabolism* / Q000473:pathology; D030541:Databases, Genetic; D015536:Down-Regulation / Q000235:genetics; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D000860:Hypoxia / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D055757:SOXE Transcription Factors / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: D012333:RNA, Messenger; D055757:SOXE Transcription Factors