A polysialic acid mimetic peptide promotes functional recovery in a mouse model of spinal cord injury.

Abstract

Contrary to lower species that recapitulate some of the developmental programs, in mammals, functional recovery after spinal cord injury is impaired by a non-permissive environment and the lack of plasticity of adult neurons. The developmental plasticity associated linear homopolymer of alpha 2,8-linked sialic acid (PolySialic Acid, PSA), represents a permissive determinant that could contribute to recovery. We previously showed that a PSA cyclic mimetic peptide (PR-21) displayed PSA-like biological functions (Torregrossa, P., Buhl, L., Bancila, M., Durbec, P., Schafer, C., Schachner, M., Rougon, G., 2004. Selection of poly-alpha 2,8-sialic acid mimotopes from a random phage peptide library and analysis of their bioactivity. J. Biol. Chem. 279, 30707-30714.). In the present study we investigated the therapeutic potential of PR-21 in young adult mice after dorsal hemisection at the T9 level. We show that PR-21 fulfills several criteria for an in vivo use as it is not toxic, not immunogenic and displays good stability in biological fluids or tissue. Delivery of PR-21 to the lesion site decreased the time of the animals' return to continence, and enhanced motor functions, sensorimotor control and coordination of hindlimbs with forelimbs when compared to a control peptide. At the cellular level, PR-21 increased serotonergic axon density at and caudal to the lesion site, and decreased reactive gliosis in vivo. In an in vitro model of reactive astrocytes, PR-21 increased NCAM expression in strongly GFAP positive cells. Our data point to the unique features of a carbohydrate mimicking peptide, and support the notion that PSA can be considered as an important factor in recovery from spinal cord injury.

• Authors: Philippe Marino, Jean-Chrétien Norreel, Melitta Schachner, Geneviève Rougon, Marie-Claude Amoureux
• Journal: Experimental neurology (Exp Neurol) Vol. 219 Issue 1 Pg. 163-74 (Sep 2009) ISSN: 1090-2430 [Electronic] United States
• PMID: 19445935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glial Fibrillary Acidic Protein
• Neural Cell Adhesion Molecule L1
• Neural Cell Adhesion Molecules
• PR-21 cyclic peptide
• Peptides
• Peptides, Cyclic
• Sialic Acids
• polysialic acid
• polysialyl neural cell adhesion molecule
• Serotonin

Topics

• Animals
• Astrocytes (drug effects, metabolism, pathology)
• Axons (drug effects, metabolism, ultrastructure)
• Cells, Cultured
• Denervation
• Disease Models, Animal
• Extracellular Matrix (metabolism)
• Glial Fibrillary Acidic Protein (metabolism)
• Gliosis (drug therapy, pathology, physiopathology)
• Mice
• Neural Cell Adhesion Molecule L1 (metabolism)
• Neural Cell Adhesion Molecules (drug effects, metabolism)
• Peptides (chemistry, pharmacology)
• Peptides, Cyclic (chemistry, pharmacology)
• Rats
• Rats, Wistar
• Recovery of Function (drug effects, physiology)
• Serotonin (metabolism)
• Sialic Acids (agonists, metabolism)
• Spinal Cord (drug effects, metabolism, physiopathology)
• Spinal Cord Injuries (drug therapy, metabolism, physiopathology)