TY - JOUR
T1 - Axon regeneration in peripheral nerves is enhanced by proteoglycan degradation
AU - Groves, Mari L.
AU - McKeon, Robert
AU - Werner, Erica
AU - Nagarsheth, Mehul
AU - Meador, William
AU - English, Arthur W.
N1 - Funding Information:
This work was supported by grant HD43356 from the USPHS. Thanks to Dr. Michael Kuttner for help with the statistical analyses and to Marlo Tan Walpole for her comments on an earlier version of the manuscript.
PY - 2005/10
Y1 - 2005/10
N2 - Regeneration of axons in the peripheral nervous system is enhanced by the removal of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans. However, some axons regenerate poorly despite such treatment, suggesting the existence of additional inhibitors. We compared the effects of enzymatic removal of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan species, heparan sulfate and keratan sulfate proteoglycans, on the regeneration of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and repaired using short segments of CF nerves harvested from wild-type littermates and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal regeneration was assayed by measuring the lengths of profiles of YFP+ axons in optical sections of the grafted nerves 1 week later. Except for grafts treated with keratanase, more and longer axon profiles were encountered in enzyme-treated grafts than in control grafts. Heparinase III treatments induced the greatest number of axons to enter into the graft. The proportions of axon profiles longer than 1000 μm were greater in grafts treated with chondroitinase ABC or heparinase I, but not with either keratanase or heparinase III. More regenerative sprouts were observed after treatment with heparinase I than any other enzymes. Treatment with a mixture of all four enzymes resulted in an enhancement of axon regeneration which was greater than that observed after treatment with any of the enzymes individually. The effects of chondroitinase ABC and heparinase III were correlated with specific GAG degradation. We believe that enzymatic removal of GAGs is especially effective in promoting the ability of regenerating axons to select their pathway in the distal stump (or nerve graft) and, in the case of chondroitinase ABC or heparinase I, it may also promote growth within that pathway.
AB - Regeneration of axons in the peripheral nervous system is enhanced by the removal of glycosaminoglycan side chains (GAGs) of chondroitin sulfate proteoglycans. However, some axons regenerate poorly despite such treatment, suggesting the existence of additional inhibitors. We compared the effects of enzymatic removal of GAGs from chondroitin sulfate proteoglycans versus two other proteoglycan species, heparan sulfate and keratan sulfate proteoglycans, on the regeneration of peripheral axons. Common fibular (CF) nerves of thy-1-YFP-H mice were cut and repaired using short segments of CF nerves harvested from wild-type littermates and pre-treated with a GAG-degrading enzyme for 1 h prior to nerve repair. Axonal regeneration was assayed by measuring the lengths of profiles of YFP+ axons in optical sections of the grafted nerves 1 week later. Except for grafts treated with keratanase, more and longer axon profiles were encountered in enzyme-treated grafts than in control grafts. Heparinase III treatments induced the greatest number of axons to enter into the graft. The proportions of axon profiles longer than 1000 μm were greater in grafts treated with chondroitinase ABC or heparinase I, but not with either keratanase or heparinase III. More regenerative sprouts were observed after treatment with heparinase I than any other enzymes. Treatment with a mixture of all four enzymes resulted in an enhancement of axon regeneration which was greater than that observed after treatment with any of the enzymes individually. The effects of chondroitinase ABC and heparinase III were correlated with specific GAG degradation. We believe that enzymatic removal of GAGs is especially effective in promoting the ability of regenerating axons to select their pathway in the distal stump (or nerve graft) and, in the case of chondroitinase ABC or heparinase I, it may also promote growth within that pathway.
KW - Chondroitin sulfate proteoglycans
KW - Heparan sulfate proteoglycans
KW - Keratan sulfate proteoglycans
KW - Mouse
KW - Nerve graft
KW - Yellow fluorescent protein
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U2 - 10.1016/j.expneurol.2005.04.007
DO - 10.1016/j.expneurol.2005.04.007
M3 - Article
C2 - 15950970
AN - SCOPUS:20644434062
SN - 0014-4886
VL - 195
SP - 278
EP - 292
JO - Experimental Neurology
JF - Experimental Neurology
IS - 2
ER -