High frequency stimulation induces sonic hedgehog release from hippocampal neurons

Sci Rep. 2017 Mar 6;7:43865. doi: 10.1038/srep43865.


Sonic hedgehog (SHH) as a secreted protein is important for neuronal development in the central nervous system (CNS). However, the mechanism about SHH release remains largely unknown. Here, we showed that SHH was expressed mainly in the synaptic vesicles of hippocampus in both young postnatal and adult rats. High, but not low, frequency stimulation, induces SHH release from the neurons. Moreover, removal of extracellular Ca2+, application of tetrodotoxin (TTX), an inhibitor of voltage-dependent sodium channels, or downregulation of soluble n-ethylmaleimide-sensitive fusion protein attachment protein receptors (SNAREs) proteins, all blocked SHH release from the neurons in response to HFS. Our findings suggest a novel mechanism to control SHH release from the hippocampal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Electric Stimulation
  • Extracellular Space / metabolism
  • HEK293 Cells
  • Hedgehog Proteins / metabolism*
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Humans
  • Microscopy, Electron, Transmission
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Rats, Sprague-Dawley
  • Sodium Channel Blockers / pharmacology
  • Synaptic Vesicles / metabolism*
  • Tetrodotoxin / pharmacology
  • Time Factors


  • Hedgehog Proteins
  • Shh protein, rat
  • Sodium Channel Blockers
  • Tetrodotoxin
  • Calcium