Hypoxia-ischemia-induced apoptotic cell death correlates with IGF-I mRNA decrease in neonatal rat brain.
Hypoxia-ischemia induces apoptotic and necrotic cell death, which results partially from persistent alterations in cellular energy homeostasis. Insulin-like growth factor I (IGF-I) is an anabolic pleiotrophic factor required by developing neurons for their optimal proliferation, differentiation, and survival. To determine how cell death and changes in IGF-I gene expression relate to the extent of hypoxia-ischemia, we evaluated the time course of apoptosis in a neonatal hypoxia-ischemia model in relation to the cellular distribution of IGF-I and IGFBP5 mRNA. Severe hypoxia-ischemia results in an immediate decrease in neuronal IGF-I and IGFBP5 mRNA. The decrease in neuronal IGF-I mRNA was concurrent with an increase in the number of apoptotic cells. It is conceivable that the immediate decrease in IGF-I gene expression may contribute to the impending neuronal death and selective vulnerability of myelinogenesis during the perinatal period.
Clawson
T F
TF
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202-5119. USA.
Vannucci
S J
SJ
Wang
G M
GM
Seaman
L B
LB
Yang
X L
XL
Lee
W H
WH
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D017209:Apoptosis; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I