Jee Hyun Yi1, Soo Ji Beak2, Seungheon Lee3, Ji Wook Jung4, Byeong C Kim2, Jong Hoon Ryu5, Dong Hyun Kim6. 1. School of Clinical Sciences, Faculty of Medicine and Dentistry, University of Bristol, Bristol, UK. 2. Chonnam-Bristol Frontier Laboratory, Biomedical Research Institute, Chonnam National University Hospital, Jebong-ro, Gwangju 501-757, Republic of Korea. 3. Department of Aquatic Biomedical Sciences, School of Marine Biomedical Science, College of Ocean Science, Jeju National University, Jeju 690-756, Republic of Korea. 4. Department of Herbal Medicinal Pharmacology, College of Herbal Bio-industry, Daegu Haany University, Kyungsan, Republic of Korea. 5. Department of Life and Nanopharmaceutical Sciences and,College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea; Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea. Electronic address: jhryu63@khu.ac.kr. 6. Department of Medicinal Biotechnology, College of Natural Resources and Life Science, Dong-A University, Busan, Republic of Korea. Electronic address: mose79@dau.ac.kr.
Abstract
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 (LTP), 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 PD198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LTP 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.
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 (LTP), 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 PD198306 blocked the DJS-induced activation of the ERK1/2/CREB/BDNF cascade and LTP 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.