Role of TrkB kinase activity in aging diaphragm neuromuscular junctions

Sarah M. Greising, Jessica M. Stowe, Gary C. Sieck, Carlos B. Mantilla

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Brain derived neurotrophic factor (BDNF) acting through the tropomyosin-related kinase receptor B (TrkB) enhances neuromuscular transmission in the diaphragm muscle of adult mice, reflecting presynaptic effects. With aging, BDNF enhancement of neuromuscular transmission is lost. We hypothesize that disrupting BDNF/TrkB signaling in early old age will reveal a period of susceptibility evident by morphological changes at neuromuscular junctions (NMJ). Adult, male TrkBF616A mice (n=25) at 6 and 18months of age, were used to examine the structural properties of diaphragm muscle NMJs (n=1097). Confocal microscopy was used to compare pre- and post-synaptic morphology and denervation following a 7day treatment with the phosphoprotein phosphatase-1 derivative 1NMPP1, which inhibits TrkB kinase activity in TrkBF616A mice vs. vehicle treatment. In early old age (18months), presynaptic terminal volume decreased compared to 6month old diaphragm NMJs (~20%). Inhibition of TrkB kinase activity significantly decreased the presynaptic terminal volume (~20%) and motor end-plate 2D planar area (~10%), independent of age group. Inhibition of TrkB kinase activity in early old age significantly reduced overlap of pre- and post-synaptic structures and increased the proportion of denervated NMJs (to ~20%). Collectively these results support a period of susceptibility in early old age when BDNF/TrkB signaling at diaphragm NMJs supports the maintenance of NMJs structure and muscle innervation.

Original languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalExperimental Gerontology
Volume72
DOIs
StatePublished - Dec 1 2015

Keywords

  • Brain derived neurotrophic factor
  • Denervation
  • Innervation
  • Motor unit
  • Tropomyosin-related kinase receptor subtype B

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

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