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Schisandrin enhances dendrite outgrowth and synaptogenesis in primary cultured hippocampal neurons
Shih-Hung Yang1, Chung-Jiuan Jeng, Chien-Hsing Chen
1Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 10051, Taiwan.
Background:
Schisandra chinensis, commonly used in Asia for tea material and traditional Chinese medicine, is presumed to enhance mental and intellectual functions. In this study, the effects and signalling mechanisms of a purified compound schisandrin, one of the lignan of Schisandra chinensis, on primary cultured hippocampal neurons were investigated.
Results:
Schisandrin treatment enhanced total dendritic length and branching complexity, both of which were significantly suppressed in the presence of specific blockers for calmodulin-dependent kinase II (CaMKII), protein kinase C epsilon (PKCε), and mitogen activated protein kinase kinase (MEK). Moreover, schisandrin induced calcium influx, and phosphorylation of CaMKII, PKCε, and MEK. Inhibition of CAMKII and PKCε attenuated the schisandrin-induced phosphorylation of PKCε and MEK, and the phosphorylation of MEK, respectively. Moreover, schisandrin also stimulated the phosphorylation of cyclic AMP responsive-element binding protein (CREB) at Ser-133, an effect that was blocked by KN93. In addition to its neuritogenic effects, schisandrin increased the numbers of postsynaptic density-95-positive and FM1-43-positive puncta in dendrites and synaptic boutons, respectively.
Conclusion:
In hippocampal neurons, schisandrin exhibits neurotrophic properties that are mediated by the CaMKII-PKCε-MEK pathway.
