title: Schisandrin enhances dendrite outgrowth and synaptogenesis in primary cultured hippocampal neurons.
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.
  
  
  CONCLUSIONS
  In hippocampal neurons, schisandrin exhibits neurotrophic properties that are mediated by the CaMKII-PKCε-MEK pathway.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei 10051, Taiwan.
authors.forename: Shih-Hung
authors.initials: SH
authors.lastname: Yang
authors.forename: Chung-Jiuan
authors.initials: CJ
authors.lastname: Jeng
authors.forename: Chien-Hsing
authors.initials: CH
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Yung-Chia
authors.initials: YC
authors.lastname: Chen
authors.forename: Seu-Mei
authors.initials: SM
authors.lastname: Wang
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1 / Q000378:metabolism; D034242:Cyclooctanes / Q000494:pharmacology*; D003712:Dendrites / Q000187:drug effects* / Q000378:metabolism; D005638:Fruit; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development; D017705:Lignans / Q000494:pharmacology*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011083:Polycyclic Compounds / Q000494:pharmacology*; D057907:Post-Synaptic Density / Q000187:drug effects* / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D032141:Schisandra / Q000737:chemistry*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D034242:Cyclooctanes; D017705:Lignans; D010936:Plant Extracts; D011083:Polycyclic Compounds; D051744:Protein Kinase C-epsilon; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020929:Mitogen-Activated Protein Kinase Kinases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C011105:schizandrin; D002118:Calcium