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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

Changes in memory retention in rats after corticosterone injection. Open circles, control rats; closed circles, rats injected with corticosterone. Arrowhead shows endpoint of rest without trial, and “−2 days” indicates the start point of resting. *p<0.01, **p<0.05 vs normal control; means ± SE, n = 9 for each group of rats.
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Figure 6: Changes in memory retention in rats after corticosterone injection. Open circles, control rats; closed circles, rats injected with corticosterone. Arrowhead shows endpoint of rest without trial, and “−2 days” indicates the start point of resting. *p<0.01, **p<0.05 vs normal control; means ± SE, n = 9 for each group of rats.

Mentions: As pyramidal cell loss in the hippocampus, which modulates memory function, was observed after injection of corticosterone, we examined the influence of corticosterone on memory function in rats. As shown in Fig. 6, control rats mostly retained their memories of the platform location throughout the experimented period. However, when rats were injected with corticosterone, they retained their memories for 4 days after resting for 48 h. However, their memories suddenly declined beginning at 5 days after the rest period. In the final test after administration of corticosterone, memory function decreased by 50–60%.


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)

Changes in memory retention in rats after corticosterone injection. Open circles, control rats; closed circles, rats injected with corticosterone. Arrowhead shows endpoint of rest without trial, and “−2 days” indicates the start point of resting. *p<0.01, **p<0.05 vs normal control; 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 6: Changes in memory retention in rats after corticosterone injection. Open circles, control rats; closed circles, rats injected with corticosterone. Arrowhead shows endpoint of rest without trial, and “−2 days” indicates the start point of resting. *p<0.01, **p<0.05 vs normal control; means ± SE, n = 9 for each group of rats.
Mentions: As pyramidal cell loss in the hippocampus, which modulates memory function, was observed after injection of corticosterone, we examined the influence of corticosterone on memory function in rats. As shown in Fig. 6, control rats mostly retained their memories of the platform location throughout the experimented period. However, when rats were injected with corticosterone, they retained their memories for 4 days after resting for 48 h. However, their memories suddenly declined beginning at 5 days after the rest period. In the final test after administration of corticosterone, memory function decreased by 50–60%.

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