Schisandrin enhances dendrite outgrowth and synaptogenesis in primary cultured hippocampal neurons

J Sci Food Agric. 2011 Mar 15;91(4):694-702. doi: 10.1002/jsfa.4238.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Cyclic Nucleotide Phosphodiesterases, Type 1 / metabolism
  • Cyclooctanes / pharmacology*
  • Dendrites / drug effects*
  • Dendrites / metabolism
  • Fruit
  • Hippocampus / drug effects*
  • Hippocampus / growth & development
  • Lignans / pharmacology*
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Neurogenesis / drug effects*
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Polycyclic Compounds / pharmacology*
  • Post-Synaptic Density / drug effects*
  • Post-Synaptic Density / metabolism
  • Presynaptic Terminals / drug effects
  • Protein Kinase C-epsilon / metabolism
  • Rats
  • Rats, Wistar
  • Schisandra / chemistry*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Cyclooctanes
  • Lignans
  • Plant Extracts
  • Polycyclic Compounds
  • Protein Kinase C-epsilon
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Mitogen-Activated Protein Kinase Kinases
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • schizandrin
  • Calcium