Prednisone induces cognitive dysfunction, neuronal degeneration, and reactive gliosis in rats

J Investig Med. 2002 Nov;50(6):458-64. doi: 10.1136/jim-50-06-06.


Background: High glucocorticoid serum levels and prednisone (PDN) therapy have been associated with depression, posttraumatic stress disorder, and some types of cognitive dysfunction in humans.

Objective: The aim of this study was to assess whether chronic (90 days) PDN administration produces disturbance in learning and memory retention associated with neuronal degeneration and cerebral glial changes.

Methods: Male Wistar rats were studied. Controls received 0.1 ml distilled water vehicle orally. The PDN group was treated orally with 5 mg/kg/d PDN, which is equivalent to moderate doses used in clinical settings. Learning and memory retention were assessed with the Morris water maze. The index of degenerated neurons as well as the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex and the CA1 hippocampus.

Results: PDN-treated rats showed a significant delay of 20% in learning and memory retention as compared with controls. In addition, in the PDN group, the neuronal degeneration index was two times higher in the prefrontal cortex, and approximately 10 times higher in the CA1 hippocampus, than in control animals. The number and cytoplasmic transformation of astrocytes were also significantly higher in the PDN group than in control animals. In the PDN-treated group, isolectin-B4-labeled microglia cells were higher in the prefrontal cortex but not in the hippocampus.

Conclusion: These results suggest that chronic exposure to PDN produces learning and memory impairment, reduces neural viability, and increases glial reactivity in cerebral regions with these cognitive functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Behavior, Animal / drug effects*
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Cell Survival / drug effects
  • Drinking
  • Gliosis / chemically induced*
  • Gliosis / pathology
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / pharmacology*
  • Learning Disabilities / chemically induced*
  • Learning Disabilities / psychology
  • Male
  • Maze Learning / drug effects
  • Memory Disorders / chemically induced*
  • Memory Disorders / psychology
  • Neurons / drug effects
  • Neurons / pathology
  • Prednisone / administration & dosage
  • Prednisone / pharmacology*
  • Rats
  • Rats, Wistar
  • Toxicity Tests


  • Glucocorticoids
  • Prednisone