title: Sevoflurane Impairs Growth Cone Motility in Dissociated Murine Neurons.
abstract: BACKGROUND
  Early postnatal exposure to general anesthetic agents causes a lasting impairment in learning and memory in animal models. One hypothesis to explain this finding is that exposure to anesthetic agents during critical points in neural development disrupts the formation of brain circuitry. Here, we explore the effects of sevoflurane on the neuronal growth cone, a specialization at the growing end of axons and dendrites that is responsible for the targeted growth that underlies connectivity between neurons.
  
  
  METHODS
  Dissociated neuronal cultures were prepared from embryonic mouse neocortex. Time-lapse images of live growth cones exposed to anesthetics were taken using differential interference contrast microscopy, and the rate of change of the area of the lamellipodia and the speed of the filopodial tip were quantified as measures of motility. The involvement of the p75 neurotropin receptor (p75NTR) was tested using inhibitors applied to the media and by a coimmunoprecipitation assay.
  
  
  RESULTS
  The rate of lamellipodial area change and filopodial tip velocity in both axonal and dendritic growth cones was significantly reduced with sevoflurane exposure between 2% and 6%. Motility could be substantially restored by treatment with Y27632 and TAT-peptide 5, which are inhibitors of Rho Kinase and p75NTR, respectively. Sevoflurane results in reduced coimmunoprecipitation of Rho-Guanosine-5'-diphosphate dissociation inhibitor after pulldown with p75NTR.
  
  
  CONCLUSIONS
  Sevoflurane interferes with growth cone motility, which is a critical process in brain circuitry formation. Our data suggest that this may occur through an action on the p75NTR, which promotes growth inhibitory signaling by the Rho pathway.
authors: *School of Medicine, Columbia University College of Physicians and Surgeons, New York, NY†Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutes, Baltimore, MD.
authors: Yun Kyoung
authors: YK
authors: Ryu
authors: Reilley P
authors: RP
authors: Mathena
authors: Sanghee
authors: S
authors: Lim
authors: Minhye
authors: M
authors: Kwak
authors: Michael
authors: M
authors: Xu
authors: Cyrus D
authors: CD
authors: Mintz
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D020439:Growth Cones / Q000187:drug effects*; D008738:Methyl Ethers / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D000077149:Sevoflurane