Chronic 1α,25-(OH) 2vitamin D 3 treatment reduces Ca 2+-mediated hippocampal biomarkers of aging

Abstract

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 1α,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.