Stress and the aging hippocampus

Front Neuroendocrinol. 1999 Jan;20(1):49-70. doi: 10.1006/frne.1998.0173.


The "glucocorticoid cascade hypothesis" of hippocampal aging has stimulated a great deal of research into the neuroendocrine aspects of aging and the role of glucocorticoids, in particular. Besides strengthening the methods for investigating the aging brain, this research has revealed that the interactions between glucocorticoids and hippocampal neurons are far more complicated than originally envisioned and involve the participation of neurotransmitter systems, particularly the excitatory amino acids, as well as calcium ions and neurotrophins. New information has provided insights into the role of early experience in determining individual differences in brain and body aging by setting the reactivity of the hypothalamopituitary-adrenal axis and the autonomic nervous system. As a result of this research and advances in neuroscience and the study of aging, we now have a far more sophisticated view of the interactions among genes, early development, and environmental influences, as well as a greater appreciation of events at the cellular and molecular levels which protect neurons, and a greater appreciation of pathways of neuronal damage and destruction. While documenting the ultimate vulnerability of the brain to stressful challenges and to the aging process, the net result of this research has highlighted the resilience of the brain and offered new hope for treatment strategies for promoting the health of the aging brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aging / pathology
  • Aging / physiology*
  • Animals
  • Cell Death / physiology
  • Glucocorticoids / physiology
  • Hippocampus / pathology
  • Hippocampus / physiology*
  • Humans
  • Neuronal Plasticity
  • Neurons / pathology
  • Sex Characteristics
  • Stress, Physiological / pathology
  • Stress, Physiological / physiopathology*


  • Glucocorticoids