Abstract
BackgroundIn the nervous system, as in other organs, Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key antioxidant enzyme involved in superoxide detoxification in normal cellular metabolism and after cell injury. Although it has been suggested that immature brain has a different susceptibility to oxidative damage than adult brain, the distribution and cell-specific expression of this enzyme in immature brain and after postnatal brain damage has not been documented.MethodsIn this study, we used immunohistochemistry and western blot to analyze the expression of Cu/Zn SOD in intact immature rat brain and in immature rat brain after an NMDA-induced excitotoxic cortical injury performed at postnatal day 9. Double immunofluorescence labelling was used to identify Cu/Zn SOD-expressing cell populations.ResultsIn intact immature brain, Cu/Zn SOD enzyme was widely expressed at high levels in neurons mainly located in cortical layers II, III and V, in the sub-plate, in the pyriform cortex, in the hippocampus, and in the hypothalamus. Glial fibrillary acidic protein-positive cells only showed Cu/Zn SOD expression in the glia limitans and in scattered cells of the ventricle walls. No expression was detected in interfascicular oligodendroglia, microglia or endothelial cells. Following excitotoxic damage, neuronal Cu/Zn SOD was rapidly downregulated (over 2–4 hours) at the injection site before neurodegeneration signals and TUNEL staining were observed. Later, from 1 day post-lesion onward, an upregulation of Cu/Zn SOD was found due to increased expression in astroglia. A further increase was observed at 3, 5 and 7 days that corresponded to extensive induction of Cu/Zn SOD in highly reactive astrocytes and in the astroglial scar.ConclusionWe show here that, in the intact immature brain, the expression of Cu/Zn SOD was mainly found in neurons. When damage occurs, a strong and very rapid downregulation of this enzyme precedes neuronal degeneration, and is followed by an upregulation of Cu/Zn SOD in astroglial cells.
Highlights
In the nervous system, as in other organs, Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key antioxidant enzyme involved in superoxide detoxification in normal cellular metabolism and after cell injury
Cerebral ischemia [7,8,9] and traumatic brain injury [10] cause a rapid and sustained increase in the formation of O2-., which is accelerated during mitochondrial dysfunction, and may result from increased activity of several cytosolic enzymes as phospholipase A2 [11] or cycloxygenase 2 (COX2) [7]
Cu/Zn superoxide dismutase expression in the immature rat brain As there is no available description of Cu/Zn SOD cellspecific expression in the immature brain, we began our study with this general description
Summary
As in other organs, Cu/Zn superoxide dismutase (Cu/Zn SOD) is a key antioxidant enzyme involved in superoxide detoxification in normal cellular metabolism and after cell injury. Are normally low due to the action of cytosolic copper zinc superoxide dismutase (Cu/Zn SOD) and mitochondrial manganese superoxide dismutase (Mn SOD) These key enzymes catalyze the dismutation of O2. Rapidly and spontaneously react to form the potent oxidant peroxynitrite (ONOO-), which is capable of nitrating tyrosine [3,4] contributing to the neuropathological process [5]. In this sense, superoxide radicals have been identified as important mediators of oxidative injury during ischemia-reperfusion and many other neurological injuries [6]. Cerebral ischemia [7,8,9] and traumatic brain injury [10] cause a rapid and sustained increase in the formation of O2-., which is accelerated during mitochondrial dysfunction, and may result from increased activity of several cytosolic enzymes as phospholipase A2 [11] or cycloxygenase 2 (COX2) [7]
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