title: The role of endothelial HIF-1 αin the response to sublethal hypoxia in C57BL/6 mouse pups.
abstract: Chronic sublethal hypoxia, a complication of premature birth, is associated with cognitive and motor handicaps. Responsiveness to and recovery from this hypoxic environment is dependent on induction of HIF-1 α in the cells affected. Microvascular endothelial-glial and microvascular endothelial-neuronal precursor interactions have been found to be dynamic and reciprocal, involving autocrine and paracrine signaling, with response and recovery correlated with baseline levels and levels of induction of HIF-1 α.To ascertain the roles of endothelial HIF-1 α in the responses of brain microvascular endothelial cells (EC) and neuronal precursors to hypoxia, we examined the effects of the presence and absence of endothelial HIF-1 α expression in culture and in cells comprising the subventricular zone (SVZ) and dentate gyrus under normoxic and hypoxic conditions. We used C57BL/6 WT and EC HIF-1 α -deficient mice and brain microvascular ECs isolated from these mice in western blots, immunofluorescence, and behavioral studies to examine the roles of EC HIF-1 α behaviors of endothelial and neuronal precursor cells (NPCs) in SVZ and hippocampal tissues under normoxic and hypoxic conditions and behaviors of these mice in open field activity tests. Analyses of ECs and SVZ and dentate gyrus tissues revealed effects of the absence of endothelial HIF-1 α on proliferation and apoptosis as well as open field activity, with both ECs and neuronal cells exhibiting decreased proliferation, increased apoptosis, and pups exhibiting gender-specific differences in open field activities. Our studies demonstrate the autocrine and paracrine effects of EC HIF-1 α-modulating proliferative and apoptotic behaviors of EC and NPC in neurogenic regions of the brain and gender-specific behaviors in normoxic and hypoxic settings.
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Michaud
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT,USA.|Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.affiliation: Department of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Couture
authors.affiliation: Department of Cardiovascular Medicine, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Girodano
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Schwartz
authors.affiliation: Department of Pathology, Yale University School of Medicine, New Haven, CT,USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Madri
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D015153:Blotting, Western; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D020547:Lateral Ventricles / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D009043:Motor Activity; D058953:Neural Stem Cells / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit