Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus
Promotion of axonal maturation and prevention of memory loss in mice by extracts of Astragalus mongholicus
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DOI：
10.1038/sj.bjp.0706865
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发表时间：
2006-11-01
影响因子：
7.3
通讯作者：
Komatsu, K.
中科院分区：
文献类型：
--
作者：
Tohda, C.;Tamura, T.;Komatsu, K.
背景和目的：具有萎缩神经突的神经元可以保持存活，因此即使在大脑的某些部分发生神经元死亡时，也可能具有再生的潜力。本研究的目的是探索即使在严重损伤的神经元中也能促进神经突再生和突触重建的药物的效果。实验方法：我们研究了黄芪提取物对注射淀粉样肽Ab（25-35）引起的小鼠认知缺陷的影响。我们还检测了提取物对Ab（25-35）损伤的培养神经元中神经突再生和突触重建的影响。蒙古黄芪提取物（1 g kg（-1）天（-1）持续15天，p.o.）逆转Ab（25-35）诱导的小鼠记忆丧失，并防止大脑皮层和海马中轴突和突触的丧失。用Ab（25-35）（10 μ M）处理诱导培养的大鼠皮层神经元的轴突萎缩和突触丢失。随后用A.蒙古黄芪提取物（100 μ g/ml）导致显著的轴突再生、神经元突触的重建和Ab（25-35）诱导的神经元死亡的预防。A.黄芪对轴突萎缩、突触丢失或神经元死亡没有影响。提取物的主要已知成分（黄芪甲苷I、II和IV）减少神经变性，但提取物的活性与这三种黄芪甲苷的含量无关。蒙古黄芪是治疗记忆障碍的重要候选物，其主要活性成分可能不是已知的蒙古黄芪皂苷。
Background and purpose: Neurons with atrophic neurites may remain alive and therefore may have the potential to regenerate even when neuronal death has occurred in some parts of the brain. This study aimed to explore effects of drugs that can facilitate the regeneration of neurites and the reconstruction of synapses even in severely damaged neurons.Experimental approach: We investigated the effects of extracts of Astragalus mongholicus on the cognitive defect in mice caused by injection with the amyloid peptide Ab(25-35). We also examined the effect of the extract on the regeneration of neurites and the reconstruction of synapses in cultured neurons damaged by Ab(25-35).Key results: A. mongholicus extract (1 g kg(-1) day(-1) for 15 days, p.o.) reversed Ab(25-35)-induced memory loss and prevented the loss of axons and synapses in the cerebral cortex and hippocampus in mice. Treatment with Ab(25-35) (10 mu M) induced axonal atrophy and synaptic loss in cultured rat cortical neurons. Subsequent treatment with A. mongholicus extract (100 mu g/ml) resulted in significant axonal regeneration, reconstruction of neuronal synapses, and prevention of Ab(25-35)-induced neuronal death. Similar extracts of A. membranaceus had no effect on axonal atrophy, synaptic loss, or neuronal death. The major known components of the extracts (astragalosides I, II, and IV) reduced neurodegeneration, but the activity of the extracts did not correlate with their content of these three astragalosides.Conclusion and implications: A. mongholicus is an important candidate for the treatment of memory disorders and the main active constituents may not be the known astragalosides.