Chronic 1α,25-(OH)2vitamin 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 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.