Rufinamide is a novel antiepileptic drug and commonly used in the treatment of Lennox-Gastaut syndrome. In the present study, we investigated effects of rufinamide on cognitive function using passive avoidance test and neurogenesis in the hippocampal dentate gyrus using Ki-67 (a marker for cell proliferation), doublecortin (DCX, a marker for neuroblast) and BrdU/NeuN (markers for newly generated mature neurons) immunohistochemistry in aged gerbils. Aged gerbils (24-month old) were treated with 1 mg/kg and 3 mg/kg rufinamide for 4 weeks. Treatment with 3 mg/kg rufinamide, not 1 mg/kg rufinamide, significantly improved cognitive function and increased neurogenesis, showing that proliferating cells (Ki-67-immunoreactive cells), differentiating neuroblasts (DCX-immunoreactive neuroblasts) and mature neurons (BrdU/NeuN-immunoreactive cells) in the aged dentate gyrus compared with those in the control group. When we examined its mechanisms, rufinamide significantly increased immunoreactivities of insulin-like growth factor-1 (IGF-1), its receptor (IGF-1R), and phosphorylated cAMP response element binding protein (p-CREB). However, rufinamide did not show any increase in immunoreactivities of brain-derived neurotrophic factor and its receptor. Therefore, our results indicate that rufinamide can improve cognitive function and increase neurogenesis in the hippocampus of the aged gerbil via increasing expressions of IGF-1, IGF-1R and p-CREB.

Rufinamide是一种新型抗癫痫药，通常用于治疗Lennox-Gastaut综合征。在本研究中，我们使用被动规避测试研究了芦丁酰胺对认知功能的影响，并使用Ki-67（细胞增殖标志物），doublecortin（DCX，神经母细胞标志物）和BrdU / NeuN（沙鼠中新生成的成熟神经元的标记）免疫组织化学。老年沙鼠（24个月大）分别用1 mg / kg和3 mg / kg的芦丁酰胺治疗4周。用3 mg / kg的芦丁酰胺而不是1 mg / kg的芦丁酰胺治疗可显着改善认知功能并增加神经发生，表明增殖细胞（Ki-67免疫反应性细胞）与对照组相比，老年齿状回中的分化神经母细胞（DCX免疫反应性神经母细胞）和成熟神经元（BrdU / NeuN免疫反应性细胞）。当我们检查其机制时，鲁芬酰胺可显着提高胰岛素样生长因子1（IGF-1），其受体（IGF-1R）和磷酸化的cAMP反应元件结合蛋白的免疫反应性（p -CREB）。但是，rufinamide并未显示脑源性神经营养因子及其受体的免疫反应性增加。因此，我们的结果表明，rufinamide可以通过增加IGF-1，IGF-1R和p - CREB的表达来改善老年沙土鼠海马的认知功能并增加其神经发生。