Antioxidant activity in the newborn brain: a luciferase mouse model

Oxidative stress in the newborn period may cause cell injury and inflammation if the antioxidant capacity is insufficient. To monitor antioxidant and inflammatory activity we examined by in vivo imaging various strains of luciferase reporter mice whose light-emitting properties were regulated by response elements or complete promoters related to oxidative stress and/or inflammation. The aim of this study is to present a model that can monitor genetic activity in vivo during pregnancy and the first 10 days of life.

One mouse strain reports the activity of nuclear factor-kappaB (NF-kappaB) activity, a transcription factor essential for modulating inflammation, apoptosis, differentiation and cell growth. A second mouse strain reports on superoxide dismutase 1-promoter activity. A third strain reports the promoter activity of gamma-glutamylcysteine synthetase, the rate limiting enzyme in glutathione production, and the last strain reports on antioxidant responsive element (ARE)/electrophil responsive element. Wild-type female mice mated with NF-kappaB mice were imaged through pregnancy to monitor intrauterine NF-kappaB activation.

Intrauterine NF-kappaB activity increased dramatically from day 17 towards labor. During the first 4 days of life luminescence measured was intense in all mice with distinct strain differences. All strains had high luminescence levels at day 1 and a considerably lower level at day 10.

This model allows investigation of the transcriptional regulation of key proteins related to oxidative stress and inflammation in pregnancy and the first days of life. With very little stress to the newborn animals genetic activity can be monitored day by day.