Neuritic regeneration and synaptic reconstruction induced by withanolide A
Neuritic regeneration and synaptic reconstruction induced by withanolide A
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DOI：
10.1038/sj.bjp.0706122
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发表时间：
2005-04-01
影响因子：
7.3
通讯作者：
Komatsu, K
中科院分区：
文献类型：
--
作者：
Kuboyama, T;Tohda, C;Komatsu, K
1我们研究了从印度草药Withania somnifera的Ashwagandha根中分离的withanolide A （WL-A）是否能再生神经突并重建严重损伤的神经元突触。我们还研究了WL-A对出现大脑神经元萎缩和突触丧失的记忆缺陷小鼠的影响。通过磷酸化神经丝- h （NF-H）、微管相关蛋白2 （MAP2）、突触体素和突触后密度-95 （PSD-95）的免疫染色分别观察轴突、树突、突触前和突触后A β (25 - 35) （10 μ M）诱导培养的大鼠皮质神经元轴突和树突萎缩，突触前和突触后丢失。随后用WL-A （1 μ M）处理，除了神经元突触前和突触后的重建外，还能诱导轴突和树突的显著再生WL-A (10 mmol kg（-1) day(-1)，连续13天，p.o.）恢复A β(25 - 35)诱导的小鼠记忆缺陷。此时，大脑皮层和海马的轴突、树突和突触的衰退基本恢复因此，WL-A是治疗神经退行性疾病的重要候选药物，因为它能够重建神经元网络。
1 We investigated whether withanolide A (WL-A), isolated from the Indian herbal drug Ashwagandha root of Withania somnifera), could regenerate neurites and reconstruct synapses in severely damaged neurons. We also investigated the effect of WL-A on memory-deficient mice showing neuronal atrophy and synaptic loss in the brain. Axons, dendrites, presynapses, and postsynapses were visualized by immunostaining for phosphorylated neurofilament-H (NF-H), microtubule-associated protein 2 (MAP2), synaptophysin, and postsynaptic density-95 (PSD-95), respectively.2 Treatment with A beta(25 - 35) (10 mu M) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A ( 1 mu M) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons.3 WL-A ( 10 mmol kg(-1) day(-1), for 13 days, p.o.) recovered A beta(25 - 35)-induced memory deficit in mice. At that time, the decline of axons, dendrites, and synapses in the cerebral cortex and hippocampus was almost recovered.4 WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.