Developmental expression of heme oxygenase-1 (HSP32) in rat brain: an immunocytochemical study

Heme oxygenase (HO) is a microsomal enzyme that oxidatively cleaves heme molecules to produce bile pigments, iron and carbon monoxide. In normal adult rat brain, HO-2 is the most abundant isozyme whereas HO-1 is present at very low levels except in select cell populations. Because its promoter region has NF-kB and AP-1 sites, heat-shock and heme-responsive elements, the HO-1 isozyme can be induced by a variety of stimuli. Since the expression and activity of several transcription factors such as NF-kB, Fos/Jun, and CREB show specific changes during development, we postulated that HO-1 expression may show similar developmental regulation. Using immunocytochemistry and Western blotting, this study demonstrates the development changes of HO-1 protein expression in normal brain from rats at postnatal day 7 (P7), P14, P21, and adult. Brain HO-1 immunoreactivity was highest at P7 in most brain regions including the white matter in areas of myelinogenesis, cerebral cortex, hippocampus, thalamus and hypothalamus and, in the blood vessel endothelial cells throughout the brain. In most regions, the adult pattern was reached by P21 with HO-1 protein localized almost exclusively to the dentate regions of hippocampus, some thalamic and hypothalamic nuclei, with little or no staining of endothelium, white matter and cortex. In a few select areas such as the substantia nigra, globus pallidus, ventromedial hypothalamic nucleus and the lateral preoptic nuclei area, little or no cellular HO-1 staining was observed at P7 whereas increased staining was found with maturation and adulthood. These results show that HO-1 protein expression is regulated in different cell types of specific regions of the rat brain during development.