Glucocorticoid Generates ROS to Induce Oxidative Injury in the Hippocampus, Leading to Impairment of Cognitive Function of Rats
Open Access
- 1 January 2010
- journal article
- Published by The Society for Free Radical Research Japan in Journal of Clinical Biochemistry and Nutrition
- Vol. 47 (3), 224-232
- https://doi.org/10.3164/jcbn.10-58
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.Keywords
This publication has 25 references indexed in Scilit:
- Elevation by Oxidative Stress and Aging of Hypothalamic-Pituitary-Adrenal Activity in Rats and Its Prevention by Vitamin EJournal of Clinical Biochemistry and Nutrition, 2009
- Increased F2-Isoprostane Levels in the Rat Brain and Plasma Caused by Oxidative Stress and Aging, and Inhibitory Effect of Vitamin EJournal of Clinical Biochemistry and Nutrition, 2006
- A randomized controlled trial of prednisone in Alzheimer’s diseaseNeurology, 2000
- Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation.The Journal of cell biology, 1992
- Oxidants and the central nervous system: some fundamental questions. Is oxidant damage relevant to Parkinson's disease, Alzheimer's disease, traumatic injury or stroke?Acta Neurologica Scandinavica, 1989
- Superoxide production from nonenzymatically glycated proteinFEBS Letters, 1988
- Developments of a water-maze procedure for studying spatial learning in the ratJournal of Neuroscience Methods, 1984
- The adrenocorticol stress-response in the aged male rat: Impairment of recovery from stressExperimental Gerontology, 1983
- Mutarotase effect on colorimetric determination of blood glucose with β-D-glucose oxidaseClinica Chimica Acta; International Journal of Clinical Chemistry, 1972
- Aging: A Theory Based on Free Radical and Radiation ChemistryJournal of Gerontology, 1956