Danggui-Jakyak-San enhances hippocampal long-term potentiation through the ERK/CREB/BDNF cascade

Ethnopharmacological relevance: Danggui-Jakyak-San (DJS), a traditional herbal prescription, has long been used to treat gerontological disorders due to insufficient blood supply. Aim of the study: Previously, we reported that DJS increased hippocampal neurogenesis and enhanced learning and memory. However, the precise mechanism of DJS and its effects on learning and memory are still not well understood. In this study, we investigated the effect of DJS on hippocampal long-term potentiation (LIP), a cellular mechanism thought to underlie learning and memory. Materials and Methods: To understand the effect of DJS on LTP, we used acute mouse hippocampal slices and delivered one train of high frequency stimulation (100 Hz, 100 pulses). Western blots were used to analyze the changes in protein levels induced by DJS. Morris water maze test was used to evaluate the effect of DJS on spatial long-term memory. Results: DJS enhanced LTP in the Schaffer-collateral pathway of the hippocampus in a concentration-dependent manner. Extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP response element-binding protein (CREB) were activated by DJS. Moreover, brain-derived neurotropic factor (BDNF) was also increased by DJS. Blockade of ERK1/2 activation with PD 198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LIP enhancement. In vivo, DJS improved spatial long-term memory and upregulated the hippocampal CREB/BDNF cascade. Conclusion: These results suggest that DJS enhances hippocampal LTP and spatial memory through the ERK/CREB/BDNF cascade. (C) 2015 Elsevier Ireland Ltd. All rights reserved.