Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats

Hiroya Sato, Takeyuki Takahashi, Kazumi Sumitani, Hirokatsu Takatsu, Shiro Urano

Research output: Contribution to journalArticle

112 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)224-232
Number of pages9
JournalJournal of Clinical Biochemistry and Nutrition
Volume47
Issue number3
DOIs
Publication statusPublished - 2010 Nov
Externally publishedYes

Fingerprint

Cognition
Glucocorticoids
Rats
Reactive Oxygen Species
Hippocampus
Corticosterone
Wounds and Injuries
Cornus
Serum
Glucose
Oxidative stress
Gluconeogenesis
Pyramidal Cells
Lipid Peroxides
Glucocorticoid Receptors
Memory Disorders
Glutathione Peroxidase
Superoxides
Catalase
Hypothalamus

Keywords

  • Cognitive deficit
  • Glucocorticoid
  • Hypothalamus-pituitary-adrenal axis
  • Neurodegeneration
  • Reactive oxygen species

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. / Sato, Hiroya; Takahashi, Takeyuki; Sumitani, Kazumi; Takatsu, Hirokatsu; Urano, Shiro.

In: Journal of Clinical Biochemistry and Nutrition, Vol. 47, No. 3, 11.2010, p. 224-232.

Research output: Contribution to journalArticle

Sato, Hiroya ; Takahashi, Takeyuki ; Sumitani, Kazumi ; Takatsu, Hirokatsu ; Urano, Shiro. / Glucocorticoid generates ROS to induce oxidative injury in the hippocampus, leading to impairment of cognitive function of rats. In: Journal of Clinical Biochemistry and Nutrition. 2010 ; Vol. 47, No. 3. pp. 224-232.
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