Sari Dwi Cahyani Ratna, Arfian Nur, Tranggono Untung, Setyaningsih Wiwit Ananda Wahyu, Romi Muhammad Mansyur, Emoto Noriaki
Department of Anatomy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Iran J Basic Med Sci. 2019 Oct;22(10):1218-1224. doi: 10.22038/ijbms.2019.29012.7002.
Impairment of hippocampus function as a center for memory processing occurs due to stress. L. (Gotu kola) is known to improve memory, intelligence, and neural protection although the precise mechanism is not well understood. This study aimed to investigate the effects of ethanol extracts of toward MAPK expression as down-stream signaling of brain-derived neurotrophic factor (BDNF).
We performed a chronic electrical stress model on 20 male Sprague Dawley rats (2 months-old, 180-200 g). Rats were divided into four groups: normal control group (Control) which received distilled water, and three treatment groups receiving oral Gotu kola ethanol extracts in oral doses of 150 mg/kg BW (CeA150), 300 mg/kg BW (CeA300), and 600 mg/kg BW (CeA600) over four weeks. Memory acquisition was assessed with Morris water maze. Hippocampus was harvested, then extracted for protein and RNA analysis. MAPK proteins (p38, ERK1/2, JNK) were measured using Western blot, meanwhile, BDNF and TrkB receptor were analyzed with real-time PCR (RT-PCR).
CeA600 group revealed improvement of memory performance as shown by reduction in time and distance parameters compared to control during escape latency test. This finding associated with significant elevation of hippocampal BDNF protein and mRNA level with up-regulation of TrkB mRNA expression in CeA600 group compared to control. Western-blot analysis showed significant up-regulation of ERK1/2 protein level in CeA600 group (<0.05) compare to control.
BDNF signaling through TrkB and ERK1/2 pathway contributes significantly to amelioration of memory performance after treatment in electrical stress model.
作为记忆处理中心的海马体功能会因应激而受损。虽然确切机制尚不完全清楚，但积雪草已知可改善记忆力、智力并具有神经保护作用。本研究旨在探讨积雪草乙醇提取物对作为脑源性神经营养因子（BDNF）下游信号的丝裂原活化蛋白激酶（MAPK）表达的影响。
我们对20只雄性Sprague Dawley大鼠（2月龄，180 - 200克）进行了慢性电应激模型实验。大鼠被分为四组：接受蒸馏水的正常对照组（Control），以及三个治疗组，在四周内分别口服剂量为150毫克/千克体重的积雪草乙醇提取物（CeA150）、300毫克/千克体重（CeA300）和600毫克/千克体重（CeA600）。用莫里斯水迷宫评估记忆获取情况。采集海马体，然后提取蛋白质和RNA进行分析。使用蛋白质印迹法测量MAPK蛋白（p38、ERK1/2、JNK），同时，用实时聚合酶链反应（RT-PCR）分析BDNF和TrkB受体。
在逃避潜伏期测试中，与对照组相比，CeA600组的时间和距离参数降低，表明记忆表现有所改善。这一发现与CeA600组中海马体BDNF蛋白和mRNA水平显著升高以及TrkB mRNA表达上调有关，与对照组相比。蛋白质印迹分析显示，与对照组相比，CeA600组ERK1/2蛋白水平显著上调（<0.05）。
在电应激模型中，BDNF通过TrkB和ERK1/2途径的信号传导对积雪草治疗后记忆表现的改善有显著贡献。
