Ginsenoside Re and Rd Enhance the Expression of Cholinergic Markers and Neuronal Differentiation in Neuro-2a Cells
Ginsenoside Re and Rd Enhance the Expression of Cholinergic Markers and Neuronal Differentiation in Neuro-2a Cells
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DOI：
10.1248/bpb.b14-00011
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发表时间：
2014-05-01
影响因子：
2
通讯作者：
Joo, Seong Soo
中科院分区：
文献类型：
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作者：
Kim, Min Soo;Yu, Jung Min;Joo, Seong Soo
阿尔茨海默病（AD）是一种以广泛的神经元缺失和神经递质乙酰胆碱（ACh）缺乏为主要特征的脑内疾病。在本研究中，我们的目的是调查是否有代表性的人参皂苷可以调节胆碱乙酰转移酶（ChAT）和囊泡乙酰胆碱转运蛋白（VAChT），这是胆碱能神经传递所需的。结果表明，Re和Rd能有效地诱导Neuro-2a细胞ChAT/VAChT基因的表达和ACh的升高。微管相关蛋白-2（MAP-2）、神经生长因子受体（p75）、p21和TrkA基因和蛋白也显著表达。此外，这两个激活的细胞外信号调节蛋白激酶（ERK）和Akt的抑制K252 a，一种选择性的Trk受体抑制剂。这些发现有力地表明Re和Rd在神经元分化和神经生长因子（NGF）-TrkA信号通路中起重要作用。高效液相色谱分析表明，口服Re和Rd成功地进入脑组织，并增加ChAT和VAChT mRNA的水平。本研究表明，Re和Rd是选择性的候选人上调胆碱能标记物的表达，这可能会对抗AD的症状和进展。
In Alzheimer's disease (AD), extensive neuronal loss and a deficiency of the neurotransmitter acetylcholine (ACh) are the major characteristics during pathogenesis in the brain. In the present study, we aimed to investigate whether representative ginsenosides from ginseng can regulate choline acetyltransferase (ChAT) and vesicular acetylcholine transporter (VAChT), which are required for cholinergic neurotransmission. Our results revealed that Re and Rd induced effectively the expression of ChAT/VAChT genes in Neuro-2a cells as well as ACh elevation. Microtubule-associated protein-2 (MAP-2), nerve growth factor receptor (p75), p21, and TrkA genes and proteins were also significantly expressed. Moreover, both activated extracelullar signal-regulated protein kinase (ERK) and Akt were inhibited by K252a, a selective Trk receptor inhibitor. These findings strongly indicate that Re and Rd play an important role in neuronal differentiation and the nerve growth factor (NGF)-TrkA signaling pathway. High performance liquid chromatography analysis showed that Re and Rd administered orally were transported successfully into brain tissue and increased the level of ChAT and VAChT mRNA. The present study demonstrates that Re and Rd are selective candidates for upregulation of the expression of cholinergic markers, which may counter the symptoms and progress of AD.