Stimulating neurite regeneration in the mammalian PNS through de-glycanation

The axons in cut nerves of a damaged body part can regenerate and even insert into a surgically attached graft. Stimulating this growth is important in medical applications as it helps to restore sensation to the affected body part.

The ability of axons to cross the surgical barrier between the proximal and distal stump is inhibited by chondroitin sulfate proteoglycans, a type of glycoprotein. These proteoglycans (and others in the Schwann cell basil lamina) have large glycosaminoglycan (GAG) side chains which inhibit growth through their large size and negative charge.

Groves et al. describe an in vivo attempt to use a number of bacterial enzymes to remove the GAG side group from the proteoglycans and thus remove the inhibition and stimulate axon growth. The enzymes they used were chondroitinase ABC, keratanase, heparinase I, and heparinase III. The researchers used thy-1-YFP-H transgenic mice because it has expresses yellow flourscent protein in the axons of motor neurons and analyzed the common fibular nerve.

In terms of the amount of regenerative sprouting, the heparinase I yielded the only significant difference from the control saline solution, however in terms of length of axon growth into the graft, chondroitinaise ABC performed the best of the enzymes.

Interestingly, when the researchers used a mixture of all of the four enzymes in equal concentrations, the resulting length of axon regeneration was significantly greater than the lengths of any of the enzymes individually. This result suggests that the different enzymes effect different facets of axonal regeneration, or that different types of neurons respond differently to different enzymes.

Reference

Groves ML, McKeon R, Werner E, Nagarsheth M, Meador W, English AW. 2005 Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation. Experimental Neurology 195: 278-292. doi:10.1016/j.expneurol.2005.04.007.