ZFIN ID: ZDB-PUB-180530-19
Phenelzine, a cell adhesion molecule L1 mimetic small organic compound, promotes functional recovery and axonal regrowth in spinal cord-injured zebrafish
Li, R., Sahu, S., Schachner, M.
Date: 2018
Source: Pharmacology, biochemistry, and behavior   171: 30-38 (Journal)
Registered Authors: Schachner, Melitta
Keywords: Axonal regrowth, L1, Phenelzine, Remyelination, Spinal cord injury, Zebrafish
MeSH Terms:
  • Animals
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Locomotion/drug effects
  • Myelin Sheath/physiology
  • Nerve Regeneration/drug effects*
  • Neural Cell Adhesion Molecule L1/metabolism*
  • Phenelzine/pharmacology*
  • Phenelzine/therapeutic use
  • Phosphorylation/drug effects
  • Recovery of Function/drug effects*
  • Spinal Cord Injuries/drug therapy
  • Spinal Cord Injuries/metabolism*
  • Spinal Cord Injuries/physiopathology*
  • Up-Regulation/drug effects
  • Zebrafish
PubMed: 29802870 Full text @ Pharmacol. Biochem. Behav.
Injury to the spinal cord initiates a cascade of cellular and molecular events that contribute to the tissue environment that is non-permissive for cell survival and axonal regrowth/sprouting in the adult mammalian central nervous system. The endogenous repair response is impaired in this generally inhibitory environment. Previous studies indicate that homophilic interactions of the neural cell adhesion molecule L1 (L1CAM) promote recovery after spinal cord injury and ameliorate neurodegenerative processes in experimental rodent and zebrafish models. In light of reports that phenelzine, a small organic compound that mimics L1, stimulates neuronal survival, neuronal migration, neurite outgrowth, and Schwann cell proliferation in vitro in a L1-dependent manner, we examined the restorative potential of phenelzine in a zebrafish model of spinal cord injury. Addition of phenelzine into the aquarium water immediately after spinal cord injury accelerated locomotor recovery and promoted axonal regrowth and remyelination in larval and adult zebrafish. Phenelzine treatment up-regulated the expression and proteolysis of L1.1 (a homolog of the mammalian recognition molecule L1) and phosphorylation of Erk in the spinal cord caudal to lesion site. By combining the results of the present study with those of other studies, we propose that phenelzine bears hopes for therapy of nervous system injuries.