Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 286, Issue -, Pages 71-77Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2018.03.007
Keywords
Aged gerbil; cAMP response element binding protein; Dentate gyrus; Insulin-like growth factor-1; Neurogenesis; Rufinamide
Funding
- Project of Scientific Research Found of Zhejiang Provincial Education Department [Y201737249]
- Natural Science Foundation of Zhejiang Province [LQ18H090003]
- Bio & Medical Technology Development Program of the NRF - the Korean government, MSIP [NRF-2015M3A9B6066835]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2017R1A2B4008403]
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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.
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