Chronic 1α,25-(OH)2vitamin D3 treatment reduces Ca2+-mediated hippocampal biomarkers of aging

Lawrence D. Brewer, Nada M. Porter, D. Steven Kerr, Philip W. Landfield, Olivier Thibault

Research output: Contribution to journalArticlepeer-review

74 Scopus citations

Abstract

Aging in the hippocampus of several species is characterized by alterations in multiple Ca2+-mediated processes, including an increase in L-type voltage-gated Ca2+ channel (L-VGCC) current, an enhanced Ca2+-dependent slow afterhyperpolarization (AHP), impaired synaptic plasticity and elevated Ca2+ transients. Previously, we found that 1α,25-dihydoxyvitamin D3 (1,25VitD), a major Ca2+ regulating hormone, down-regulates L-VGCC expression in cultured hippocampal neurons. Here, we tested whether in vivo treatment of aged F344 rats with 1,25VitD would reverse some of the Ca2+ -mediated biomarkers of aging seen in hippocampal CA1 neurons. As previously reported, L-VGCC currents and the AHP were larger in aged than in young neurons. Treatment with 1,25VitD over 7 days decreased L-VGCC activity in aged rats, as well as the age-related increase in AHP amplitude and duration. In addition, reduced L-VGCC activity was correlated with reduced AHPs in the same animals. These data provide direct evidence that 1,25VitD can regulate multiple Ca2+-dependent processes in neurons, with particular impact on reducing age-related changes associated with Ca2+ dysregulation. Thus, these results may have therapeutic implications and suggest that 1,25VitD, often taken to maintain bone health, may also retard some consequences of brain aging.

Original languageEnglish
Pages (from-to)277-286
Number of pages10
JournalCell Calcium
Volume40
Issue number3
DOIs
StatePublished - Sep 2006

Bibliographical note

Funding Information:
This work was supported by Grants AG04542, AG10836 and AG20251 from the National Institute on Aging. We thank Michael Bridges and Michelle Sama for their technical assistance, and Dr. Amy Dowling for reading an earlier version of this manuscript.

Keywords

  • Afterhyperpolarization
  • Aging
  • Calcium channel
  • Hippocampus
  • Patch-clamp
  • Vitamin D

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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