| Distribution and Expression of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) Receptor Subunits in Moderate Hypoxic Newborn Piglet Brain |
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Na Yeon Kim, Woo Taek Ki |
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Department of Pediatrics, College of Medicine, Dongguk University, Kyongju, Korea |
| 중등도 저산소증이 유발된 신생자돈 뇌에서α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) 수용체의 분포와 발현 |
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김나연, 김우택 |
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동국대학교 의과대학 소아과학교실 |
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| Abstract |
Purpose
: The mechanism of hypoxic damage is mainly intracellular influx of calcium ions through the glutamate ionotropic receptor(NMDA, AMPA/kainate). This study was performed to determine alterations in distribution and expression of AMPA receptor subunits after 1-hour of moderate hypoxia in the newborn piglet brain, in a state of mild to moderate perinatal hypoxic-ischemic encephalopathy.
Methods
: Ten newborn piglets were mechanically ventilated with a mixture of 21% oxygen and 79% nitrous oxide at PaO2 over 80mmHg for 30min. Thereafter, control group(n=5) was ventilated with 21% oxygen for 1-hour, and hypoxic group(n=5) was ventilated with 6% oxygen at PaO2 below 25mmHg for 1-hour. Concentrations of protein, adenosine triphosphate(ATP) and phosphocreatine were determined. The proteins were immunostained with anti-rat glutamate receptor 1(GluR1), anti-rat GluR2/3 and anti-rat GluR4 antibody.
Results
: Hypoxia(PaO2 20±1mmHg) and acidosis(pH 7.06±0.09) developed significantly in the hypoxic group compared to the control group(PaO2 104±4mmHg, pH 7.44±0.03, respectively, P<0.01). Concentrations of ATP(2.84±1.28μmol/kg brain, P<0.05) and phosphocreatine(0.78±1.07μmol/kg brain, P<0.001) were significantly reduced compared to the control group(5.04±0.25μmol/kg brain, 4.03±0.31μmol/kg brain, respectively). The protein contents of GluR1 and GluR2/3 subunits were ordered; hippocampus > cerebral cortex, thalamus, basal ganglia, hypothalamus > white matter, cerebellum, and the protein contents of GluR4 subunits were observed in the cerebellum only. The distribution of GluR1, GluR2/3, and GluR4 subunits between the hypoxic group and control group were similar.
Conclusion
: GluR1 and GluR2/3 subunits were highly distributed in the hippocampus and cere bral cortex, and GluR4 subunits in the cerebellum. These regions may be the most vulnerable to excitotoxic injury. In addition, AMPA receptor subunits did not change after 1-hour of moderate hypoxia. |
| Key Words:
Glutamate, α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor subunit, Moderate hypoxia, In vivo |
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