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Neuritic regeneration and synaptic reconstruction induced by withanolide A
Author(s) -
Kuboyama Tomoharu,
Tohda Chihiro,
Komatsu Katsuko
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706122
Subject(s) - synaptophysin , neuroscience , postsynaptic potential , biology , hippocampus , neurofilament , neurite , synaptic plasticity , axon , immunostaining , immunohistochemistry , biochemistry , receptor , in vitro , immunology
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 β (25–35) (10 μ M ) induced axonal and dendritic atrophy, and pre‐ and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL‐A (1 μ 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 μ mol kg −1 day −1 , for 13 days, p.o.) recovered A β (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.British Journal of Pharmacology (2005) 144 , 961–971. doi: 10.1038/sj.bjp.0706122