Neuritic regeneration and synaptic reconstruction induced by withanolide A.
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 A beta(25-35) (10 microM) induced axonal and dendritic atrophy, and pre- and postsynaptic loss in cultured rat cortical neurons. Subsequent treatment with WL-A (1 microM) induced significant regeneration of both axons and dendrites, in addition to the reconstruction of pre- and postsynapses in the neurons. WL-A (10 micromol 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. WL-A is therefore an important candidate for the therapeutic treatment of neurodegenerative diseases, as it is able to reconstruct neuronal networks.
Kuboyama
Tomoharu
T
Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
Tohda
Chihiro
C
Komatsu
Katsuko
K
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D018517:Plant Roots; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D032341:Withania
D010936:Plant Extracts