Disrupted synaptic development in the hypoxic newborn brain.
Infants born prematurely risk significant life-long cognitive disability, representing a major pediatric health crisis. The neuropathology of this cohort is accurately modeled in mice subjected to sublethal postnatal hypoxia. Massively parallel transcriptome analysis using cDNA microchips (9,262 genes), combined with immunohistochemical and protein assays, reveals that sublethal hypoxia accentuates genes subserving presynaptic function, and it suppresses genes involved with synaptic maturation, postsynaptic function, and neurotransmission. Other significantly affected pathways include those involved with glial maturation, vasculogenesis, and components of the cortical and microtubular cytoskeleton. These patterns reveal a global dysynchrony in the maturation programs of the hypoxic developing brain, and offer insights into the vulnerabilities of processes that guide early postnatal cerebral maturation.
Curristin
Sheila M
SM
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA.
Cao
Anjun
A
Stewart
William B
WB
Zhang
Heping
H
Madri
Joseph A
JA
Morrow
Jon S
JS
Ment
Laura R
LR
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D017209:Apoptosis; D001273:Atmosphere Exposure Chambers; D001925:Brain Damage, Chronic / Q000209:etiology / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000648:ultrastructure; D018076:DNA, Complementary / Q000235:genetics; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000502:physiology; D020869:Gene Expression Profiling; D000860:Hypoxia; D002534:Hypoxia, Brain / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D008222:Lymphokines / Q000502:physiology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008870:Microtubules / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009836:Oligodendroglia / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D013312:Stress, Physiological / Q000235:genetics; D013569:Synapses / Q000473:pathology*; D009435:Synaptic Transmission; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D018076:DNA, Complementary; D016228:Endothelial Growth Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors