Role of extracellular signal-regulated kinase in rubrofusarin-enhanced cognitive functions and neurite outgrowth

Biomedicine & Pharmacotherapy

卷:147

Se Jin Park¹  Ji Woong Choi²  Wan-Seob Cho³  Huiyoung Kwon³  Byeong C. Kim⁴  Kyoung Ja Kwon⁵  Jong Hoon Ryu⁶  Jieun Jeon⁷  Eunbi Cho⁷  Chan Young Shin⁷  Se Jin Jeon⁸  Dong Hyun Kim⁹  Tamanna Jahan Mony⁹ 

[1] School of Medicine and Center for Neuroscience Research, Konkuk University, Seoul 05029, Republic of Korea;

[2] College of Pharmacy and Gachon Institute of Pharmaceutical Sciences, Gachon University, Incheon 21936, Republic of Korea;

[3] Department of Health Sciences, The Graduate School of Dong-A University, Busan 49315, Republic of Korea;

[4] Department of Neurology, Chonnam National University Medical School, Gwangju, Republic of Korea;

[5] Department of Neuroscience, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea;

[6] Department of Oriental Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Seoul 02447, Republic of Korea;

[7] Department of Pharmacology and Department of Advanced Translational Medicine, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea;

[8] School of Natural Resources and Environmental Sciences, Kangwon National University, Chuncheon, Republic of Korea;

关键词: Rubrofusarin;    Learning and memory;    Neurogenesis;    Long-term potentiation;    Extracellular signal-regulated kinase;   

DOI  :  

来源: DOAJ

【 摘 要 】

Memory-enhancing agents have long been required for various reasons such as for obtaining a good score in a test in the young and for retaining memory in the aged. Although many studies have found that several natural products may be good candidates for memory enhancement, there is still a need for better agents. The present study investigated whether rubrofusarin, an active ingredient in Cassiae semen, enhances learning and memory in normal mice. Passive avoidance and Morris water maze tests were performed to determine the memory-enhancing ability of rubrofusarin. To investigate synaptic function, hippocampal long-term potentiation (LTP) was measured. Western blotting was performed to determine protein levels. To investigate neurite outgrowth, DCX immunohistochemistry and cell culture were utilised. Rubrofusarin (1, 3, 10, 30 mg/kg) enhanced memory in passive avoidance and Morris water maze tests. Moreover, rubrofusarin ameliorated scopolamine-induced memory impairment. In the rubrofusarin-treated group, high-frequency stimulation induced higher LTP in the hippocampal Schaffer-collateral pathway compared to the control group. The rubrofusarin-treated group showed a higher number of DCX-positive immature neurons with an increase in the length of dendrites compared to the control group in the hippocampal dentate gyrus region. In vitro experiments showed that rubrofusarin facilitated neurite outgrowth in neuro2a cells through extracellular signal-regulated kinase (ERK). Finally, we found that extracellular signal-regulated kinase (ERK) is required for rubrofusarin-induced enhancement of neurite outgrowth, learning and memory. These results demonstrate that rubrofusarin enhances learning and memory and neurite outgrowth, and these might need activation of ERK pathway.

【 授权许可】

Unknown