The calcium hypothesis for Alzheimer's disease: Insights from animal and human studies

John F Disterhoft*, L. T. Thompson, Craig Weiss, J. R. Moyer, E. Van der Zee, M. Carrillo, M. Kronforst-Collins, J. Power

*Corresponding author for this work

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The calcium hypothesis of aging and neural degeneration is discussed in the context of its potential application to Alzheimer's disease. Calcium homeostasis in neurons and the effect of aging on calcium-related homeostatic mechanisms are extremely important potential contributors to alterations which may lead to neuronal deterioration and, ultimately, cell death. Eyeblink conditioning is a behavioral model which we have used to probe hippocampal changes in learning and aging. Hippocampal neurons demonstrate increased excitability after associative learning, as evidenced by reductions in the calcium-dependent afterhyperpolarization and spike frequency accomodation. Aging hippocampal neurons show reduced excitability by these indices, correlated with impaired eyeblink conditioning ability in aging rabbits. The calcium channel antagonist nimodipine enhances excitability in aging hippocampal neurons and enhances behavioral learning rate in aging rabbits. A similar behavioral effect has been observed after nimodipine administration in humans. Eyeblink conditioning and other hippocampally-dependent behaviors are being adapted for the mouse to enable further systematic examination of the calcium hypothesis of Alzheimer's disease in a powerful animal model which complements earlier work.

Original languageEnglish (US)
Pages (from-to)121-131
Number of pages11
JournalNeuroscience Research Communications
Volume17
Issue number2
StatePublished - Sep 12 1995

Keywords

  • 48 references
  • 6 figures
  • Aging
  • Ca antagonists
  • Hippocampus
  • Human
  • Mouse
  • Rabbit
  • Trace eyeblink conditioning

ASJC Scopus subject areas

  • Neuroscience(all)

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    Disterhoft, J. F., Thompson, L. T., Weiss, C., Moyer, J. R., Van der Zee, E., Carrillo, M., Kronforst-Collins, M., & Power, J. (1995). The calcium hypothesis for Alzheimer's disease: Insights from animal and human studies. Neuroscience Research Communications, 17(2), 121-131.