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Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.

Publication ,  Journal Article
Alexander, GM; Huang, YZ; Soderblom, EJ; He, X-P; Moseley, MA; McNamara, JO
Published in: J Neurochem
February 2017

Vagal Nerve Stimulation (VNS) Therapy® is a United States Food and Drug Administration approved neurotherapeutic for medically refractory partial epilepsy and treatment-resistant depression. The molecular mechanisms underlying its beneficial effects are unclear. We hypothesized that one mechanism involves neuronal activity-dependent modifications of central nervous system excitatory synapses. To begin to test this hypothesis, we asked whether VNS modifies the activity of neurons in amygdala and hippocampus. Neuronal recordings from adult, freely moving rats revealed that activity in both amygdala and hippocampus was modified by VNS immediately after its application, and changes were detected following 1 week of stimulation. To investigate whether VNS modifies the proteome of excitatory synapses, we established a label-free, quantitative liquid chromatography-tandem mass spectrometry workflow that enables global analysis of the constituents of the postsynaptic density (PSD) proteome. PSD proteins were biochemically purified from amygdala/piriform cortex of VNS- or dummy-treated rats following 1-week stimulation, and individual PSD protein levels were quantified by liquid chromatography-tandem mass spectrometry analysis. We identified 1899 unique peptides corresponding to 425 proteins in PSD fractions, of which expression levels of 22 proteins were differentially regulated by VNS with changes greater than 150%. Changes in a subset of these proteins, including significantly increased expression of neurexin-1α, cadherin 13 and voltage-dependent calcium channel α2δ1, the primary target of the antiepileptic drug gabapentin, and decreased expression of voltage-dependent calcium channel γ3, were confirmed by western blot analysis of PSD samples. These results demonstrate that VNS modulates excitatory synapses through regulating a subset of the PSD proteome. Our study reveals molecular targets of VNS and point to possible mechanisms underlying its beneficial effects, including activity-dependent formation of excitatory synapses.

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Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

February 2017

Volume

140

Issue

4

Start / End Page

629 / 644

Location

England

Related Subject Headings

  • Vagus Nerve Stimulation
  • Synapses
  • Rats, Sprague-Dawley
  • Rats
  • Proteome
  • Piriform Cortex
  • Neurons
  • Neurology & Neurosurgery
  • Male
  • Excitatory Postsynaptic Potentials
 

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Alexander, G. M., Huang, Y. Z., Soderblom, E. J., He, X.-P., Moseley, M. A., & McNamara, J. O. (2017). Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex. J Neurochem, 140(4), 629–644. https://doi.org/10.1111/jnc.13931
Alexander, Georgia M., Yang Zhong Huang, Erik J. Soderblom, Xiao-Ping He, M Arthur Moseley, and James O. McNamara. “Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.J Neurochem 140, no. 4 (February 2017): 629–44. https://doi.org/10.1111/jnc.13931.
Alexander GM, Huang YZ, Soderblom EJ, He X-P, Moseley MA, McNamara JO. Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex. J Neurochem. 2017 Feb;140(4):629–44.
Alexander, Georgia M., et al. “Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex.J Neurochem, vol. 140, no. 4, Feb. 2017, pp. 629–44. Pubmed, doi:10.1111/jnc.13931.
Alexander GM, Huang YZ, Soderblom EJ, He X-P, Moseley MA, McNamara JO. Vagal nerve stimulation modifies neuronal activity and the proteome of excitatory synapses of amygdala/piriform cortex. J Neurochem. 2017 Feb;140(4):629–644.
Journal cover image

Published In

J Neurochem

DOI

EISSN

1471-4159

Publication Date

February 2017

Volume

140

Issue

4

Start / End Page

629 / 644

Location

England

Related Subject Headings

  • Vagus Nerve Stimulation
  • Synapses
  • Rats, Sprague-Dawley
  • Rats
  • Proteome
  • Piriform Cortex
  • Neurons
  • Neurology & Neurosurgery
  • Male
  • Excitatory Postsynaptic Potentials