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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

154 Citations (Scopus)


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
Issue number3
Publication statusPublished - 2010 Nov
Externally publishedYes


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

ASJC Scopus subject areas

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


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