Pathological changes of distal motor neurons after complete spinal cord injury

Traumatic spinal cord injury (SCI) causes serious disruption of neuronal circuits that leads to motor functional deficits. Regeneration of disrupted circuits back to their original target is necessary for the restoration of function after SCI, but the pathophysiological condition of the caudal spinal cord has not been sufficiently studied. Here we investigated the histological and biological changes in the distal part of the injured spinal cord, using a mice model of complete thoracic SCI in the chronic stage (3 months after injury). Atrophic changes were widely observed in the injured spinal cord both rostral and caudal to the lesion, but the decrease in area was mainly in the white matter in the rostral spinal cord while both the white and gray matter decreased in the caudal spinal cord. The number of the motor neurons was maintained in the chronic phase of injury, but the number of presynaptic boutons decreased in the lumbar motor neurons caudal to the lesion. Using laser microdissection, to investigate gene expressions in motor neurons caudal to the lesion, we observed a decrease in the expressions of neuronal activity markers. However, we found that the synaptogenic potential of postsynapse molecules was maintained in the motor neurons after SCI with the expression of acetylcholine-related molecules actually higher after SCI. Collectively, our results show that the potential of synaptogenesis is maintained in the motor neurons caudal to the lesion, even though presynaptic input is decreased. Although researches into SCI concentrate their effort on the lesion epicenter, our findings suggest that the area caudal to the lesion could be an original therapeutic target for the chronically injured spinal cord.

• Publication year

  2019

• Venue

  Molecular Brain

• Publication date

  2019-01-09

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/s13041-018-0422-3PMID 30626449PMCID 6327522
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Postsynapse molecules retained synaptogenic potential after spinal cord injury, and acetylcholine-related molecules were expressed at higher levels.

  Confidence 0.93

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• Motor neurons caudal to the lesion showed decreased expression of neuronal activity markers.

  Confidence 0.94

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• The number of motor neurons was maintained in the chronic phase, but presynaptic boutons were reduced on lumbar motor neurons caudal to the lesion.

  Confidence 0.95

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• Atrophic changes were observed both rostral and caudal to the lesion, with white matter loss predominating rostrally and both white and gray matter decreasing caudally.

  Confidence 0.97

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review

• acetylcholine-related molecules

  molecule

  Molecules linked to acetylcholine signaling or cholinergic function in motor neurons.

  Aliases: cholinergic-related molecules

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• caudal spinal cord

  anatomical structure

  The spinal cord region distal to the injury site, below the lesion.

  Aliases: distal spinal cord

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• chronic stage

  timepoint

  The late post-injury timepoint examined here, 3 months after spinal cord injury.

  Aliases: chronic phase

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• complete thoracic spinal cord injury

  injury model

  A mouse model of complete thoracic spinal cord injury used to examine chronic distal spinal cord changes.

  Aliases: complete thoracic SCI, thoracic SCI

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• lumbar motor neurons

  cell type

  Motor neurons in the lumbar spinal cord that were analyzed on the caudal side of the lesion.

  Aliases: lumbar MNs

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• neuronal activity markers

  molecular marker

  Genes or molecular markers used to indicate neuronal activity in the analyzed motor neurons.

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• postsynapse molecules

  molecule

  Postsynaptic molecules associated with synapse formation and maintenance in motor neurons.

  Aliases: postsynaptic molecules

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review
• presynaptic boutons

  cellular structure

  Presynaptic contact structures associated with synaptic input onto motor neurons.

  Aliases: presynaptic terminals

  박진우 (dztg5apj7m) extractionB (s683577b42) reviewimjlk (vdp8mqzes2) review

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