Neuritic regeneration and synaptic reconstruction induced by withanolide A
Authors
Tomoharu Kuboyama
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Chihiro Tohda
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
Katsuko Komatsu
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
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.
Treatment with Aβ(25–35) (10 μM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 μM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons.
WL-A (10 μmol kg−1 day−1, for 13 days, p.o.) recovered Aβ(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.
WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.
Keywords: Axon, dendrite, presynapse, postsynapse, Morris water maze, Aβ(25–35), Withania somnifera, Ashwagandha, withanolide
Author Biographies
Tomoharu Kuboyama, Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
Katsuko Komatsu, Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
st Century COE Program, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan
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