title: St. John's Wort enhances the synaptic activity of the nucleus of the solitary tract.
abstract: OBJECTIVE
  St. John's Wort (SJW) extract, which is commonly used to treat depression, inhibits the reuptake of several neurotransmitters, including glutamate, serotonin, norepinephrine, and dopamine. Glutamatergic visceral vagal afferents synapse upon neurons of the solitary tract (NST); thus, the aim of this study was to evaluate whether SJW extract modulates glutamatergic neurotransmission within the NST.
  
  
  METHODS
  We used live cell calcium imaging to evaluate whether SJW and its isolated components hypericin and hyperforin increase the excitability of prelabeled vagal afferent terminals synapsing upon the NST. We used voltage-clamp recordings of spontaneous miniature excitatory postsynaptic currents (mEPSCs) to evaluate whether SJW alters glutamate release from vagal afferents onto NST neurons.
  
  
  RESULTS
  Our imaging data show that SJW (50 μg/mL) increased the intracellular calcium levels of stimulated vagal afferent terminals compared with the bath control. This increase in presynaptic vagal afferent calcium by the extract coincides with an increase in neurotransmitter release within the nucleus of the solitary tract, as the frequency of mEPSCs is significantly higher in the presence of the extract compared with the control. Finally, our imaging data show that hyperforin, a known component of SJW extract, also significantly increases terminal calcium levels.
  
  
  CONCLUSIONS
  These data suggest that SJW extract can significantly increase the probability of glutamate release from vagal afferents onto the NST by increasing presynaptic calcium. The in vitro vagal afferent synapse with NST neurons is an ideal model system to examine the mechanism of action of botanical agents on glutamatergic neurotransmission.
authors.affiliation: Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: Katie M
authors.initials: KM
authors.lastname: Vance
authors.affiliation: Biotech Center, Rutgers University, New Brunswick, NJ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Ribnicky
authors.affiliation: Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors.forename: Gerlinda E
authors.initials: GE
authors.lastname: Hermann
authors.affiliation: Laboratory of Autonomic Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA. Electronic address: Richard.rogers@pbrc.edu.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Rogers
mesh_terms: D000818:Animals; D000873:Anthracenes; D002118:Calcium / Q000378:metabolism; D003863:Depression; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism*; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism; D010569:Perylene / Q000031:analogs & derivatives / Q000494:pharmacology; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D020318:Rats, Long-Evans; D017552:Solitary Nucleus / Q000187:drug effects*; D013569:Synapses; D009435:Synaptic Transmission / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology; D014630:Vagus Nerve / Q000378:metabolism
chemical_list: D000873:Anthracenes; D010936:Plant Extracts; D013729:Terpenes; D018698:Glutamic Acid; D010569:Perylene; C004965:hypericin; D010696:Phloroglucinol; C001654:hyperforin; D002118:Calcium
keywords: Botanical; Calcium imaging; EPSC; Electrophysiology; NST; Presynaptic; Vagus nerve