Naslov
Sialidase enhances spinal axon outgrowth.

Autori
Yang, Lynda JS. ; Lorenzini, Ileana ; Vajn, Katarina ; Schramm, Lawrence P. ; Schnaar, Ronald L.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Skup
Annual Conference of the Society for Glycobiology

Mjesto i datum
Boston (MA), Sjedinjene Američke Države, 09.11.2005. - 12.11.2005

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
sialidase; sialoglycoconjugates; axonal outgrowth

Sažetak
The adult central nervous system, including the spinal cord, is a profoundly inhibitory environment for axon outgrowth, severely limiting recovery after traumatic nervous system injury. Axons have the capacity to regenerate, but are inhibited from doing so by molecules that accumulate or persist at injury sites, including chondroitin sulfate proteoglycan (CSPG), Nogo, oligodendrocyte-myelin glycoprotein (OMgp), and myelin-associated glycoprotein (MAG) [1]. These inhibitors, found on residual myelin or astrocytes, bind to receptors on nerve cell axons to initiate intracellular signals that halt axon outgrowth. Glycans are involved in each inhibitory cascade. CSPG requires glycosaminoglycan chains for inhibition, OMgp and Nogo receptor are GPI-anchored proteins, and MAG is a sialic acid binding lectin (Siglec-4). In vitro, treatment with chondroitinase, sialidase or phosphatidylinositol-specific phospholipase C (PI-PLC) enhances axon outgrowth on inhibitory substrata, and chondroitinase ABC delivery to the site of experimental spinal cord injury enhances recovery in rats [2]. We used an animal model of brachial plexus (nerve root) avulsion injury in the rat to extend these studies. Our model mimicked disruption of nerve roots upon traumatic neck and shoulder displacement. Such injuries are not uncommon in difficult childbirths and motorcycle accidents, resulting in profound loss of limb use. Recent therapy includes peripheral nerve grafts at the avulsion site. Treatments that improve axon outgrowth into the graft are expected to enhance recovery. To test the efficacy of glycobiology tools in this model, chondroitinase ABC, PI-PLC, and sialidase were delivered to the graft site and spinal axon outgrowth into the graft was quantified. Ventral spinal roots (C8) in rats were cut, then a peripheral nerve graft was inserted at the injury site. Using an osmotic pump, saline (control), chondroitinase ABC (0.5 U/ml), PI-PLC (2 or 20 U/ml) or sialidase (0.1 or 0.4 U/ml) was delivered to the graft site for two weeks. Spinal axons extending well into the peripheral nerve graft were then retrogradely labeled with a fluorescent dye. Tissues were fixed, the spinal cord was dissected, and axon outgrowth into the graft was quantified by measuring the number of fluorescently labeled spinal neurons. Marked enhancement (>2.5-fold, p < 0.01) of axon outgrowth into peripheral nerve grafts was observed in animals treated with chondroitinase ABC or 0.4 U/ml sialidase, whereas PI-PLC or 0.1 U/ml sialidase were without significant effect. These results indicate that sialidase and chondroitinase enhance axon regeneration, and that treatments that modify CSPG or sialoglycoconjugates may aid recovery after nervous system injury. Supp. by NIH grants NS046669, HL16315 & Univ. of Mich. Dept. of Neurosurgery. IL is a Hopkins PREP Scholar (GM064124). KV supp. by the Croatian Ministry of Science.

Izvorni jezik
Engleski

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