2001 Fiscal Year Final Research Report Summary
Apoptosis and neuronal cell death induced by chronic hypoxemia in fetal sheep brain
| Project/Area Number |
12671060
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Tohoku University |
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Principal Investigator |
MUROTSUKI Jun Tohoku University Hospital, Lecturer, 医学部・附属病院, 講師 (50239555)
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| Co-Investigator(Kenkyū-buntansha) |
SASANO Hironobu Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (50187142)
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| Project Period (FY) |
2000 – 2001
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| Keywords | neuronal death / apoptosis / fetal sheep / chronic hypoxemia |
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| Research Abstract |
We tested the hypothesis that chronic hypoxemia modulates NO production of the fetal brain by altering its gene and protein expression. Chronically instrumented preterm fetal sheep were made hypoxemic by placental embolization for 21 days. Fetal oxygen content was measured to determine the level of hypoxemia. The expression of both eNOS and nNOS proteins and mRNA and enzyme activities of fetal sheep cerebrum were measured and compared between normoxic and hypoxemic animals. Our results show that in utero hypoxemia downregulates both Ca 2 q dependent NOS activity and expression of eNOS protein and mRNA in the fetal sheep brain. In contrast, hypoxemia increased nNOS protein and mRNA levels in the cerebrum. This suggests that chronic hypoxemia has an opposing effect on eNOS and nNOS gene regulation. We propose that increased nNOS activity during chronic hypoxemia may excessively stimulate the neurons and contribute to fetal brain injury. On the other hand, downregulation of eNOS activity and expression may compromise the neuroprotective effect of eNOS and, therefore, further exacerbate brain injury.
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