Motoneuron glutamatergic receptor expression following recovery from cervical spinal hemisection

Heather M. Gransee, Maria A. Gonzalez Porras, Wen Zhi Zhan, Gary C Sieck, Carlos Bernardo Mantilla

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Cervical spinal hemisection at C2 (SH) removes premotor drive to phrenic motoneurons located in segments C3–C5 in rats. Spontaneous recovery of ipsilateral diaphragm muscle activity is associated with increased phrenic motoneuron expression of glutamatergic N-methyl-D-aspartate (NMDA) receptors and decreased expression of α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptors. Glutamatergic receptor expression is regulated by tropomyosin-related kinase receptor subtype B (TrkB) signaling in various neuronal systems, and increased TrkB receptor expression in phrenic motoneurons enhances recovery post-SH. Accordingly, we hypothesize that recovery of ipsilateral diaphragm muscle activity post-SH, whether spontaneous or enhanced by adenoassociated virus (AAV)-mediated upregulation of TrkB receptor expression, is associated with increased expression of glutamatergic NMDA receptors in phrenic motoneurons. Adult male Sprague-Dawley rats underwent diaphragm electromyography electrode implantation and SH surgery. Rats were injected intrapleurally with AAV expressing TrkB or GFP 3 weeks before SH. At 14 days post-SH, the proportion of animals displaying recovery of ipsilateral diaphragm activity increased in AAV–TrkB-treated (9/9) compared with untreated (3/5) or AAV–GFP-treated (4/10; P < 0.027) animals. Phrenic motoneuron NMDA NR1 subunit mRNA expression was approximately fourfold greater in AAV–TrkB- vs. AAV–GFP-treated SH animals (P < 0.004) and in animals displaying recovery vs. those not recovering (P < 0.005). Phrenic motoneuron AMPA glutamate receptor 2 (GluR2) subunit mRNA expression decreased after SH, and, albeit increased in animals displaying recovery vs. those not recovering, levels remained lower than control. We conclude that increased phrenic motoneuron expression of glutamatergic NMDA receptors is associated with spontaneous recovery after SH and enhanced recovery after AAV–TrkB treatment. J. Comp. Neurol. 525:1192–1205, 2017.

Original languageEnglish (US)
Pages (from-to)1192-1205
Number of pages14
JournalJournal of Comparative Neurology
Volume525
Issue number5
DOIs
StatePublished - Apr 1 2017

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Keywords

  • diaphragm muscle
  • neuroplasticity
  • neurotrophin
  • phrenic motoneuron
  • RRID:RGD_5508397
  • RRID:SCR_010038
  • RRID:SCR_014325
  • spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)

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