Detrimental effects of chronic hypothalamic-pituitary-adrenal axis activation: From obesity to memory deficits

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131 Scopus citations


Increasing evidence suggests that the detrimental effects of glucocorticoid (GC) hypersecretion occur by activation of the hypothalamic- pituitary-adrenal (HPA) axis in several human pathologies, including obesity, Alzheimer's disease, AIDS dementia, and depression. The different patterns of response by the HPA axis during chronic activation are an important consideration in selecting an animal model to assess HPA axis function in a particular disorder. This article will discuss how chronic HPA axis activation and GC hypersecretion affect hippocampal function and contribute to the development of obesity. In the brain, the hippocampus has the highest concentration of GC receptors. Chronic stress or corticosterone treatment induces neuropathological alterations, such as dendritic atrophy in hippocampal neurons, which are paralleled by cognitive deficits. Excitatory amino acid (EAA) neurotransmission has been implicated in chronic HPA axis activation. EAAs play a major role in neuroendocrine regulation. Hippocampal dendritic atrophy may involve alterations in EAA transporter function, and decreased EAA transporter function may also contribute to chronic HPA axis activation. Understanding the molecular mechanisms of HPA axis activation will likely advance the development of therapeutic interventions for conditions in which GC levels are chronically elevated.

Original languageEnglish (US)
Pages (from-to)1-22
Number of pages22
JournalMolecular Neurobiology
Issue number1
StatePublished - Jan 1 1998
Externally publishedYes


  • Adrenal gland
  • Amygdala
  • Arginine vasopressin
  • Chronic stress
  • Cognitive deficits
  • Excitatory amino acids
  • Glucocorticoids
  • Hippocampus
  • Hypothalamus
  • Obesity

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience


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