Changes in glutathione in the hippocampus of rats injected with kainate: depletion in neurons and upregulation in glia

Abstract

The aim of the present study was to elucidate the distribution of glutathione immunoreactivity in the normal hippocampus and after kainate-induced neuronal injury. A specific antibody was used that recognizes both the reduced (GSH) and oxidized (GSSG) forms of glutathione. Immunoreactivity to glutathione was observed in neurons, but few immunolabeled glial cells were observed in the normal hippocampus. After kainate injection, a decrease in glutathione immunoreactivity was observed in pyramidal neurons from as early as 1 day after injection. In contrast, dense staining to glutathione was observed in large numbers of reactive astrocytes at 3 days to 6 weeks after kainate injection. This suggests upregulation of glutathione synthesis in these cells. One possibility is that the high content of glutathione is protective to reactive astrocytes. Another possibility is that the high glutathione concentration in reactive astrocytes may be protective to neurons around the glial scar.

Searching for Mechanisms of N-Methyl-d-Aspartate-Induced Glutathione Efflux in Organotypic Hippocampal Cultures

“…Alternatively, the efflux have different cellular origin. Glutathione is present in both neurons and glia (29,30,(82)(83)(84)(85)(86), but as no functional NMDA receptors appear to be located on hippocampal glia cells (87), the most straightforward explanation for the increase in glutathione efflux is neuronal release. However, it cannot be excluded that NMDA-receptor stimulation induces a release of a substance from neurons that evokes glutathione release from the glial cells.…”

Inhibitors of Brain Phospholipase A2Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders

“…This stimulation of cPLA 2 activity in neuron-enriched cultures can be blocked by a nonspecific cPLA 2 inhibitor, quinacrine , a PlsEtn-PLA 2 inhibitor, BEL , a sPLA 2 inhibitor, 12-episclaradial , or by a KA/AMPA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione . During KA neurotoxicity, the increased cPLA 2 immunoreactivity is accompanied by an increase in the 4-HNE immunoreactivity and a decrease in glutathione immunoreactivity (Ong et al, 2000) in hippocampus, indicating alterations in cellular redox. The reduction in glutathione levels may be due either to the formation of a 4-HNE-glutathione adduct or to decrease in cysteine uptake caused by KA-mediated neurotoxicity.…”

Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis

“…After a 48 h incubation with the primary antibody (1:200) at 4°C, sections were incubated with the secondary biotinylated antisera for 1 h, and immersed in avidin-biotin-peroxidase complex for 1 h. 3,3=-Diaminobenzidine was used as a chromogen. The glutathione antibody (Hjelle et al, 1994;Ong et al, 2000;Kim et al, 2003) has been described elsewhere. Antibodies raised against GSH also recognized the oxidized form (Hjelle et al, 1994).…”

“…Antibodies raised against GSH also recognized the oxidized form (Hjelle et al, 1994). Thus, attempts to raise antibodies that react with GSSG but not with the reduced form have not met with success (Hjelle et al, 1994;Ong et al, 2000;Kim et al, 2003). It is likely, however, that the reduced form is responsible for the major share of the immunocytochemical signal, as the reduced form is known to predominate over the oxidized form (Meister and Anderson, 1983;Meister 1994).…”