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Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus, Leading to Impairment of Cognitive Function of Rats.

Sato H, Takahashi T, Sumitani K, Takatsu H, Urano S - J Clin Biochem Nutr (2010)

Bottom Line: These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus.Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus.The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Chemistry, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohtoh-ku, Tokyo 135-8548, Japan.

ABSTRACT
The present study attempted to clarify whether over-secretion of glucocorticoids in the serum caused by increased hypothalamus-pituitary-adrenal activity induces oxidative stress in the rat brain, and how the stress causes the emergence of cognitive deficits. When rats were subcutaneously injected with corticosterone, lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus in association with a decrease in activity of antioxidative enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus. After administration of corticosterone to rats, glucose and superoxide levels in the serum increased markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus. Rats injected with corticosterone showed marked deficits in memory function. The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.

No MeSH data available.


Related in: MedlinePlus

Superoxide generation in rat serum caused by corticosterone injection. A, control; B, rats injected by corticosterone; C, Fe(NO3)3-added A; D, Fe(NO3)3-added B. *p<0.05 vs A, **p<0.01 vs B; means ± SE, n = 9 for each group of rats.
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Figure 4: Superoxide generation in rat serum caused by corticosterone injection. A, control; B, rats injected by corticosterone; C, Fe(NO3)3-added A; D, Fe(NO3)3-added B. *p<0.05 vs A, **p<0.01 vs B; means ± SE, n = 9 for each group of rats.

Mentions: As it has been reported that human serum albumin and/or polypeptides are glycated by glucose nonenzymatically in vitro, followed by superoxide generation, and that generation of superoxide was accelerated by the presence of ferric ions [24], the increased serum glucose levels in this study most likely produced superoxide via glycation reactions with serum protein of rats administered corticosterone. As shown in Fig. 4, when rats were injected with corticosterone, levels of superoxide in the serum increased markedly compared to controls (Fig. 4, column B). Control sera mixed with ferric ions showed high levels of superoxide (Fig. 4, column C), but following addition of ferric ions to sera from rats injected with corticosterone, superoxide levels were more markedly increased (Fig. 4, column D). These results indicate that increased glucose in the serum after corticosterone administration reacted nonenzymatically with serum proteins via a glycation reaction to induce excess levels of superoxide.


Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus, Leading to Impairment of Cognitive Function of Rats.

Sato H, Takahashi T, Sumitani K, Takatsu H, Urano S - J Clin Biochem Nutr (2010)

Superoxide generation in rat serum caused by corticosterone injection. A, control; B, rats injected by corticosterone; C, Fe(NO3)3-added A; D, Fe(NO3)3-added B. *p<0.05 vs A, **p<0.01 vs B; means ± SE, n = 9 for each group of rats.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2966932&req=5

Figure 4: Superoxide generation in rat serum caused by corticosterone injection. A, control; B, rats injected by corticosterone; C, Fe(NO3)3-added A; D, Fe(NO3)3-added B. *p<0.05 vs A, **p<0.01 vs B; means ± SE, n = 9 for each group of rats.
Mentions: As it has been reported that human serum albumin and/or polypeptides are glycated by glucose nonenzymatically in vitro, followed by superoxide generation, and that generation of superoxide was accelerated by the presence of ferric ions [24], the increased serum glucose levels in this study most likely produced superoxide via glycation reactions with serum protein of rats administered corticosterone. As shown in Fig. 4, when rats were injected with corticosterone, levels of superoxide in the serum increased markedly compared to controls (Fig. 4, column B). Control sera mixed with ferric ions showed high levels of superoxide (Fig. 4, column C), but following addition of ferric ions to sera from rats injected with corticosterone, superoxide levels were more markedly increased (Fig. 4, column D). These results indicate that increased glucose in the serum after corticosterone administration reacted nonenzymatically with serum proteins via a glycation reaction to induce excess levels of superoxide.

Bottom Line: These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus.Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus.The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.

View Article: PubMed Central - PubMed

Affiliation: Division of Biological Chemistry, Shibaura Institute of Technology, 3-7-5 Toyosu, Kohtoh-ku, Tokyo 135-8548, Japan.

ABSTRACT
The present study attempted to clarify whether over-secretion of glucocorticoids in the serum caused by increased hypothalamus-pituitary-adrenal activity induces oxidative stress in the rat brain, and how the stress causes the emergence of cognitive deficits. When rats were subcutaneously injected with corticosterone, lipid hydroperoxides and protein carbonyls increased markedly in the hippocampus in association with a decrease in activity of antioxidative enzymes, such as superoxide dismutase, catalase and glutathione peroxidase. These results suggest that high-level corticosterone in the serum induces reactive oxygen species (ROS), leading to oxidative damage in the hippocampus. After administration of corticosterone to rats, glucose and superoxide levels in the serum increased markedly. Furthermore, pyramidal cell apoptosis was observed to accompany the loss of glucocorticoid receptors at the cornus ammonis 1 region of the hippocampus. Rats injected with corticosterone showed marked deficits in memory function. The present results imply that ROS generated from the glycation reaction of increased glucose levels caused by gluconeogenesis activation through glucocorticoid with proteins in the serum attack the hippocampus to induce neurodegeneration, resulting in cognitive deficits in rats.

No MeSH data available.


Related in: MedlinePlus