Developmental patterns of NF-kappa B activation during acute hypoxia in the caudal brainstem of the rat

NF-kappaB, an ubiquitous transcription factor which plays a major role in t he regulation of stress-related genes, is activated during environmental hy poxia in the dorsocaudal brainstem of adult rats. To examine the developmen tal pattern of NF-kappaB basal activity in the brainstem and the response t o hypoxia, electromobility shift assays and immunohistochemical staining fo r the P65 subunit of NF-kappaB were performed in caudal brainstem samples o f rats at 2, 5, 10, 15, and 60 days postnatal age, following normoxic or hy poxic (1 h in 10% O-2) exposures. In addition, the expression of I kappaB-a lpha, and I kappaB kinases (ikk)-alpha and -beta was also examined using We stern blots. Basal NF-kappaB nuclear activity and nuclear P65 immunoreactiv ity increased with maturation. In contrast, hypoxia induced enhanced activa tion of NF-kappaB and nuclear translocation of P65 in youngest animals. Exp ression of both I kappaB-alpha and ikk-alpha was highest in the mon immatur e rats, and decreased with postnatal age. In contrast, ikk-beta expression was unchanged over time. We conclude that NF-kappaB activity in caudal brai nstem is developmentally regulated, and that hypoxia-induced NF-kappaB acti vation is more prominent in youngest rats. We postulate that postnatal regu lation of NF-kappaB complex expression and function may underlie fundamenta l genomic processes mediating developmental changes in neuronal hypoxic tol erance. (C) 2001 Elsevier Science B.V. All rights reserved.