Functional motor recovery from motoneuron axotomy is compromised in mice with defective corticospinal projections

PLoS One. 2014 Jul 8;9(7):e101918. doi: 10.1371/journal.pone.0101918. eCollection 2014.

Abstract

Brachial plexus injury (BPI) and experimental spinal root avulsion result in loss of motor function in the affected segments. After root avulsion, significant motoneuron function is restored by re-implantation of the avulsed root. How much this functional recovery depends on corticospinal inputs is not known. Here, we studied that question using Celsr3|Emx1 mice, in which the corticospinal tract (CST) is genetically absent. In adult mice, we tore off right C5-C7 motor and sensory roots and re-implanted the right C6 roots. Behavioral studies showed impaired recovery of elbow flexion in Celsr3|Emx1 mice compared to controls. Five months after surgery, a reduced number of small axons, and higher G-ratio of inner to outer diameter of myelin sheaths were observed in mutant versus control mice. At early stages post-surgery, mutant mice displayed lower expression of GAP-43 in spinal cord and of myelin basic protein (MBP) in peripheral nerves than control animals. After five months, mutant animals had atrophy of the right biceps brachii, with less newly formed neuromuscular junctions (NMJs) and reduced peak-to-peak amplitudes in electromyogram (EMG), than controls. However, quite unexpectedly, a higher motoneuron survival rate was found in mutant than in control mice. Thus, following root avulsion/re-implantation, the absence of the CST is probably an important reason to hamper axonal regeneration and remyelination, as well as target re-innervation and formation of new NMJ, resulting in lower functional recovery, while fostering motoneuron survival. These results indicate that manipulation of corticospinal transmission may help improve functional recovery following BPI.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axotomy
  • Brachial Plexus / injuries
  • Female
  • GAP-43 Protein / metabolism
  • Male
  • Mice, Transgenic
  • Motor Neurons / physiology*
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / physiopathology
  • Nerve Fibers, Myelinated / physiology
  • Nerve Regeneration*
  • Neuromuscular Junction / physiopathology
  • Pyramidal Tracts / abnormalities
  • Recovery of Function

Substances

  • GAP-43 Protein

Grant support

The National Natural Science Foundation of China (81171152, L. Zhou), National Basic Research Program of China (973 Program, 2011CB504402), Foundation for High-level Talents in Higher Education of Guangdong (50524005), Project of Internation as well as Hong Kong, Macao & Taiwan Science and Technology Cooperation Innovation Platform in Universities in Guangdong Province (2013gjhz0002), the Programme of Introducing Talents of Discipline to Universities (B14036) and Fundamental Research Funds for the Central Universities (21614603). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.