Brain, behavior, and immunity · 2009
Neuregulin-1, the fetal endothelium, and brain damage in preterm newborns.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Hoffmann Insa, Bueter Wolfgang, Zscheppang Katja, Brinkhaus Maria-Jantje, Liese Andrea, Riemke Stefan, Dörk Thilo, Dammann Olaf, Dammann Christiane E L
Аннотация
OBJECTIVE: To assess the potential role for Neuregulin-1 (NRG1) as a systemic endogenous protector in the setting of perinatal inflammatory brain damage.
METHODS: We measured NRG1-protein and mRNA levels in human umbilical venous endothelial cells (HUVECs) of different gestational ages at various durations of exposure to lipopolysaccharide (LPS). In parallel, we genotyped the donor individuals for SNP8NRG221533, a disease-related single nucleotide polymorphism in the 5' region upstream of the NRG1 sequence. Intracellular NRG1 localization was visualized by confocal microscopy. Furthermore we analyzed the relationship between SNP8NRG221533 genotype and neurodevelopmental outcome in children born preterm.
RESULTS: We observed a positive dose-response-relationship between NRG1-mRNA and intracellular protein levels with both advancing gestational age and duration of LPS exposure in HUVECs. The presence of allele C at the SNP8NRG221533 locus was associated with an increased cellular production of NRG1 in HUVECs, and with a significantly reduced risk for cerebral palsy and developmental delay in children born preterm.
INTERPRETATION: In conclusion, our data indicate that gestational age, duration of LPS exposure, and the SNP8NRG221533 genotype affect NRG1 levels. Our results support the hypothesis that NRG1 may qualify as an endogenous protector during fetal development.
METHODS: We measured NRG1-protein and mRNA levels in human umbilical venous endothelial cells (HUVECs) of different gestational ages at various durations of exposure to lipopolysaccharide (LPS). In parallel, we genotyped the donor individuals for SNP8NRG221533, a disease-related single nucleotide polymorphism in the 5' region upstream of the NRG1 sequence. Intracellular NRG1 localization was visualized by confocal microscopy. Furthermore we analyzed the relationship between SNP8NRG221533 genotype and neurodevelopmental outcome in children born preterm.
RESULTS: We observed a positive dose-response-relationship between NRG1-mRNA and intracellular protein levels with both advancing gestational age and duration of LPS exposure in HUVECs. The presence of allele C at the SNP8NRG221533 locus was associated with an increased cellular production of NRG1 in HUVECs, and with a significantly reduced risk for cerebral palsy and developmental delay in children born preterm.
INTERPRETATION: In conclusion, our data indicate that gestational age, duration of LPS exposure, and the SNP8NRG221533 genotype affect NRG1 levels. Our results support the hypothesis that NRG1 may qualify as an endogenous protector during fetal development.
Предметные рубрики MeSH
BrainCells, CulturedEndothelial CellsEndothelium, VascularEnzyme-Linked Immunosorbent AssayGenotypeGestational AgeHumansInfant, NewbornInfant, PrematureLeukomalacia, PeriventricularLipopolysaccharidesMicroscopy, ConfocalNeuregulin-1Polymorphism, Single NucleotideReverse Transcriptase Polymerase Chain ReactionUmbilical Veins