Hippocampal calcium dysregulation at the nexus of diabetes and brain aging

Olivier Thibault, Katie L. Anderson, Chris Demoll, Lawrence D. Brewer, Philip W. Landfield, Nada M. Porter

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations


Recently it has become clear that conditions of insulin resistance/metabolic syndrome, obesity and diabetes, are linked with moderate cognitive impairment in normal aging and elevated risk of Alzheimer's disease. It appears that a common feature of these conditions is impaired insulin signaling, affecting the brain as well as peripheral target tissues. A number of studies have documented that insulin directly affects brain processes and that reduced insulin signaling results in impaired learning and memory. Several studies have also shown that diabetes induces Ca2+ dysregulation in neurons. Because brain aging is associated with substantial Ca2+ dyshomeostasis, it has been proposed that impaired insulin signaling exacerbates or accelerates aging-related Ca2+ dyshomeostasis. However, there have been few studies examining insulin interactions with Ca2+ regulation in aging animals. We have been testing predictions of the Ca 2+ dysregulation/diabetes/brain aging hypothesis and have found that insulin and insulin-sensitizers (thiazolidinediones) target several hippocampal Ca2+-related processes affected by aging. The drugs appear able to reduce the age-dependent increase in Ca2+ transients and the Ca 2+ -sensitive afterhyperpolarization. Thus, while additional testing is needed, the results to date are consistent with the view that strategies that enhance insulin signaling can counteract the effect of aging on Ca2+ dysregulation.

Original languageEnglish
Pages (from-to)34-43
Number of pages10
JournalEuropean Journal of Pharmacology
Issue number1-3
StatePublished - 2013

Bibliographical note

Funding Information:
Research described here was supported by NIH Grants AG020268 and AG033649 . The sponsor had no involvement in the study design, collection, analysis or interpretation of the data.


  • Afterhyperpolarization
  • Aging
  • Cognition
  • Imaging
  • Learning
  • Thiazolidinediones

ASJC Scopus subject areas

  • Pharmacology


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