A Small Organic Compound Mimicking the L1 Cell Adhesion Molecule Promotes Functional Recovery after Spinal Cord Injury in Zebrafish

Sahu, S., Zhang, Z., Li, R., Hu, J., Shen, H., Loers, G., Shen, Y., Schachner, M.
Molecular neurobiology   55(1): 859-878 (Journal)
Registered Authors
Schachner, Melitta
Axonal regrowth, Cell adhesion molecule L1, Spinal cord injury, Tacrine, Zebrafish
MeSH Terms
  • Animals
  • Creatine Kinase/metabolism
  • Gliosis/pathology
  • Larva/drug effects
  • Larva/metabolism
  • Lasers
  • Locomotion/drug effects
  • Myelin Basic Protein/metabolism
  • Neural Cell Adhesion Molecule L1/genetics
  • Neural Cell Adhesion Molecule L1/metabolism*
  • PTEN Phosphohydrolase/metabolism
  • Phosphatidylinositol 3-Kinases/metabolism
  • Phosphorylation/drug effects
  • Photons
  • Proto-Oncogene Proteins c-akt/metabolism
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Recovery of Function*/drug effects
  • Signal Transduction/drug effects
  • Small Molecule Libraries/pharmacology*
  • Spinal Cord/pathology
  • Spinal Cord Injuries/pathology
  • Spinal Cord Injuries/physiopathology*
  • Tacrine/pharmacology*
  • Tacrine/therapeutic use
  • Time Factors
  • Tumor Suppressor Protein p53/metabolism
  • Zebrafish/metabolism*
28070857 Full text @ Mol. Neurobiol.
Tacrine is a small organic compound that was discovered to mimic the functions of the neural cell adhesion molecule L1 by promoting the cognate functions of L1 in vitro, such as neuronal survival, neuronal migration, neurite outgrowth, and myelination. Based on studies indicating that L1 enhances functional recovery in different central and peripheral nervous system disease paradigms of rodents, it deemed interesting to investigate the beneficial role of tacrine in the attractive zebrafish animal model, by evaluating functional recovery after spinal cord injury. To this aim, larval and adult zebrafish were exposed to tacrine treatment after spinal cord injury and monitored for locomotor recovery and axonal regrowth. Tacrine promoted the rapid recovery of locomotor activities in both larval and adult zebrafish, enhanced regrowth of severed axons and myelination, and reduced astrogliosis in the spinal cords. Tacrine treatment upregulated the expression of L1.1 (a homolog of the mammalian recognition molecule L1) and enhanced the L1.1-mediated intracellular signaling cascades in the injured spinal cords. These observations lead to the hope that, in combination with other therapeutic approaches, this old drug may become a useful reagent to ameliorate the deficits resulting from acute and chronic injuries of the mammalian nervous system.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes