Chronic 1α,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 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 1 alpha,25-dihydoxyvitamin D-3 (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. (c) 2006 Elsevier Ltd. All rights reserved.