title: Mild intermittent hypoxia does not induce stress responses in the neonatal rat brain.
abstract: We previously demonstrated that intermittent hypoxia evokes persistent changes in extracellular striatal dopamine, locomotor activity and executive function, using a rodent model emulating apnea of prematurity in which rat pups are exposed to 20-second bursts of hypoxic gas mix containing 10% oxygen (60 events/h; 6 h/day) from postnatal days 7 to 11. To determine whether subtle repetitive hypoxic insults also induce expression of stress-related genes, we employed real-time RT-PCR to assay gene transcription in neonatal rats subjected to the same paradigm. In addition, we also measured expression of stress-induced transcripts in an age-matched cohort following a more severe oxidative stressor: permanent focal ischemia. Four transcripts were elevated following the ischemic insult: heat shock protein 70 (Hsp70), CL100, nurr77, and heme oxygenase-1. In contrast, these transcripts were not regulated in the majority of neonatal rats exposed to an intermittent hypoxia protocol. Hsp70 was strongly induced, and CL100 and nurr77 were slightly induced in only 2 of 11 post-hypoxic rats compared to controls. These data demonstrate that a single ischemic event elicits expression of specific stress-related genes, whereas 5 days of brief intermittent hypoxic insults typically do not. Thus, it is unlikely that the neurochemical and behavioral morbidity observed in juvenile and adult rodents exposed to intermittent hypoxia during a critical period of brain development are related to stress-induced changes in gene expression.
authors.affiliation: Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. vboss@comcast.net
authors.forename: Valerie
authors.initials: V
authors.lastname: Boss
authors.forename: Augusto
authors.initials: A
authors.lastname: Sola
authors.forename: Tong-Chun
authors.initials: TC
authors.lastname: Wen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Decker
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000235:genetics; D054638:Dual Specificity Phosphatase 1; D005260:Female; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D000860:Hypoxia / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054638:Dual Specificity Phosphatase 1; C517021:Dusp1 protein, rat; D017027:Protein Tyrosine Phosphatases