Chronic 1alpha,25-(OH)2 vitamin D3 treatment reduces Ca2+ -mediated hippocampal biomarkers of aging.
Aging in the hippocampus of several species is characterized by alterations in multiple Ca(2+)-mediated processes, including an increase in L-type voltage-gated Ca(2+) channel (L-VGCC) current, an enhanced Ca(2+)-dependent slow afterhyperpolarization (AHP), impaired synaptic plasticity and elevated Ca(2+) transients. Previously, we found that 1alpha,25-dihydoxyvitamin D(3) (1,25VitD), a major Ca(2+) 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 Ca(2+) -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 Ca(2+)-dependent processes in neurons, with particular impact on reducing age-related changes associated with Ca(2+) 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.
Brewer
Lawrence D
LD
Department of Molecular and Biomedical Pharmacology, University of Kentucky, 800 Rose Street, MS-310, University of Kentucky Medical Center, Lexington, 40536-0298, USA.
Porter
Nada M
NM
Kerr
D Steven
DS
Landfield
Philip W
PW
Thibault
Olivier
O
D000375:Aging / Q000502:physiology*; D000818:Animals; D015415:Biomarkers; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002118:Calcium / Q000097:blood; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D004553:Electric Conductivity; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344
D015415:Biomarkers; D020746:Calcium Channels, L-Type; D002117:Calcitriol; D002118:Calcium