BDNF/TrkB signaling regulates HNK-1 carbohydrate expression in regenerating motor nerves and promotes functional recovery after peripheral nerve repair

Kirsten A. Eberhardt, Andrey Irintchev, Abdulhakeem A. Al-Majed, Olga Simova, Thomas Brushart, Tessa Gordon, Melitta Schachner

Research output: Contribution to journalArticle

Abstract

Functional recovery after peripheral nerve injury is often poor despite high regenerative capacity of peripheral neurons. In search for novel treatments, brief electrical stimulation of the acutely lesioned nerve has recently been identified as a clinically feasible approach increasing precision of axonal regrowth. The effects of this stimulation appear to be mediated by BDNF and its receptor, TrkB, but the down-stream effectors are unknown. A potential candidate is the HNK-1 carbohydrate known to be selectively reexpressed in motor but not sensory nerve branches of the mouse femoral nerve and to enhance growth of motor but not sensory axons in vitro. Here, we show that short-term low-frequency electrical stimulation (1 h, 20 Hz) of the lesioned and surgically repaired femoral nerve in wild-type mice causes a motor nerve-specific enhancement of HNK-1 expression correlating with previously reported acceleration of muscle reinnervation. Such enhanced HNK-1 expression was not observed after electrical stimulation in heterozygous BDNF or TrkB-deficient mice. Accordingly, the degree of proper reinnervation of the quadriceps muscle, as indicated by retrograde labeling of motoneurons, was reduced in TrkB+/- mice compared to wild-type littermates. Also, recovery of quadriceps muscle function, evaluated by a novel single-frame motion analysis approach, and axonal regrowth into the distal nerve stump, assessed morphologically, were considerably delayed in TrkB+/- mice. These findings indicate that BDNF/TrkB signaling is important for functional recovery after nerve repair and suggest that up-regulation of the HNK-1 glycan is linked to this phenomenon.

Original languageEnglish (US)
Pages (from-to)500-510
Number of pages11
JournalExperimental Neurology
Volume198
Issue number2
DOIs
Publication statusPublished - Apr 2006

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Keywords

  • BDNF
  • Femoral nerve
  • HNK-1 carbohydrate
  • Motion analysis
  • Motoneuron
  • Mouse
  • Regeneration
  • TrkB

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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