Mild intermittent hypoxia does not induce stress responses in the neonatal rat brain.
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.
Boss
Valerie
V
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA. vboss@comcast.net
Sola
Augusto
A
Wen
Tong-Chun
TC
Decker
Michael J
MJ
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
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