Brewer Lawrence D, Porter Nada M, Kerr D Steven, Landfield Philip W, Thibault Olivier
Department of Molecular and Biomedical Pharmacology, University of Kentucky, 800 Rose Street, MS-310, University of Kentucky Medical Center, Lexington, 40536-0298, USA.
Cell Calcium. 2006 Sep;40(3):277-86. doi: 10.1016/j.ceca.2006.04.001. Epub 2006 Jun 14.
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.
几种物种海马体的衰老特征是多种钙介导过程发生改变，包括L型电压门控钙通道（L-VGCC）电流增加、钙依赖性慢后超极化（AHP）增强、突触可塑性受损以及钙瞬变升高。此前，我们发现1α,25-二羟基维生素D3（1,25VitD），一种主要的钙调节激素，可下调培养的海马神经元中L-VGCC的表达。在此，我们测试了用1,25VitD对衰老的F344大鼠进行体内治疗是否会逆转海马CA1神经元中一些衰老的钙介导生物标志物。如先前报道，老年神经元中的L-VGCC电流和AHP比年轻神经元中的更大。用1,25VitD治疗7天可降低老年大鼠的L-VGCC活性，以及与年龄相关的AHP幅度和持续时间的增加。此外，L-VGCC活性降低与同一只动物中AHP的降低相关。这些数据提供了直接证据，表明1,25VitD可以调节神经元中多种钙依赖性过程，对减少与钙失调相关的年龄相关变化具有特别影响。因此，这些结果可能具有治疗意义，并表明常用于维持骨骼健康的1,25VitD也可能延缓大脑衰老的一些后果。
