The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2004
The effects of hypoxia on growth cones in the ovine fetal brain.
СтатьяПоддержка службы здравоохранения СШАНазвание и аннотация: Перевод в очереди
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Morgan B L G, Chao C R
Аннотация
OBJECTIVE: This study was designed to investigate the effects of hypoxia on neural process proliferation by studying its effects on growth cone tubulin and insulin-like growth factor (IGF)-I receptor content.
METHODS: Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO2) of 20% to 6% by addition of nitrogen to the inhaled gas mixture for a period of 4 h of reduced oxygen intake. Fetal arterial blood was sampled after the maternal FiO2 and oxygen were stable for >5 min at maternal FiO2 of 20% to 6%. Controls were obtained from normoxic fetuses whose ewes had similar surgery and were kept at an FiO2 of 20% throughout the experiment. Growth cones were isolated from the fetal cerebrum and cerebellum. alpha-tubulin and IGF-I receptors were quantified by immunoblotting. Tubulin and IGF-I receptor mRNA expressions were quantified by real-time polymerase chain reaction.
RESULTS: Maternal nitrogen breathing reduced fetal arterial pH from 7.32+/-0.06 to 6.99+/-0.02 (p<0.001). Hypoxia increased IGF-I receptors from 143+/-10 to 327+/-14 (p<0.001) and from 272+/-26 to 396+/-34 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. It also increased alpha-tubulin from 713+/-30 to 1873+/-126 (p<0.001) and from 780+/-34 to 2362+/-79 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. Expression of IGF-I receptor mRNA increased significantly in the hypoxic animals both in the cerebrum and the cerebellum, but there was no change in expression of alpha-tubulin mRNA.
CONCLUSIONS: This increase in IGF-I receptor expression and growth cone content may be an adaptive response to hypoxia to maintain neurite growth by facilitating binding of IGF-I. Hypoxia also increased the growth cone level of alpha-tubulin but did not increase its mRNA expression, which may indicate an inability to polymerize tubulin and build microtubules.
METHODS: Six fetal lambs were catheterized in the brachial artery and vein. Maternal oxygenation was reduced in steps from a fractional inspired oxygen concentration (FiO2) of 20% to 6% by addition of nitrogen to the inhaled gas mixture for a period of 4 h of reduced oxygen intake. Fetal arterial blood was sampled after the maternal FiO2 and oxygen were stable for >5 min at maternal FiO2 of 20% to 6%. Controls were obtained from normoxic fetuses whose ewes had similar surgery and were kept at an FiO2 of 20% throughout the experiment. Growth cones were isolated from the fetal cerebrum and cerebellum. alpha-tubulin and IGF-I receptors were quantified by immunoblotting. Tubulin and IGF-I receptor mRNA expressions were quantified by real-time polymerase chain reaction.
RESULTS: Maternal nitrogen breathing reduced fetal arterial pH from 7.32+/-0.06 to 6.99+/-0.02 (p<0.001). Hypoxia increased IGF-I receptors from 143+/-10 to 327+/-14 (p<0.001) and from 272+/-26 to 396+/-34 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. It also increased alpha-tubulin from 713+/-30 to 1873+/-126 (p<0.001) and from 780+/-34 to 2362+/-79 (p<0.001) fluorescence units/microg protein in the cerebrum and cerebellum, respectively. Expression of IGF-I receptor mRNA increased significantly in the hypoxic animals both in the cerebrum and the cerebellum, but there was no change in expression of alpha-tubulin mRNA.
CONCLUSIONS: This increase in IGF-I receptor expression and growth cone content may be an adaptive response to hypoxia to maintain neurite growth by facilitating binding of IGF-I. Hypoxia also increased the growth cone level of alpha-tubulin but did not increase its mRNA expression, which may indicate an inability to polymerize tubulin and build microtubules.