Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.6.4 (chondroitinase)
2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chondroitin sulfates have been implicated in the promotion and in the inhibition of axon growth. In the zebrafish embryo, chondroitin sulfates are present at the interface of the somites and the notochord where spinal motor axons extend ventrally to establish the midsegmental ventral motor nerves. Injection of chondroitinase ABC prior to motor axon outgrowth effectively removed all chondroitin sulfate immunoreactivity and induced abnormal axonal outgrowth in many (39%) of the ventral motor nerves. The most common abnormality was the formation of side branches, approximately half of which extended posteriorly, the others anteriorly. The effect was specific to the removal of chondroitin sulfates, since injections of vehicle solution or of heparinase III did not affect the ventral motor nerves. Electron microscopic examination demonstrated that the injections caused no damage to spinal cord, somite, and notochord. This suggests that chondroitin sulfates normally constrain the outgrowth of the ventral motor nerves. Consistent with this hypothesis, injections of soluble chondroitin sulfates, either as a mixture or individually, led to truncated or missing ventral motor nerves. Truncations were most frequent after injection of chondroitin sulfate-B (up to 23%) while chondroitin sulfate-A had a lesser, and chondroitin sulfate-C no apparent, effect.
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PMID:Chondroitin sulfates affect the formation of the segmental motor nerves in zebrafish embryos. 1077 2

We examined whether enzymatic digestion of chondroitin sulfate (CS) promoted the axonal regeneration of neurons in Clarke's nucleus (CN) into a peripheral nerve (PN) graft following injury of the spinal cord. After hemisection at T11, a segment of PN graft was implanted at the lesion site. Either vehicle, brain-derived neurotrophic factor (BDNF) or chondroitinase ABC was applied at the implantation site. The postoperative survival period was 4 weeks. Treatment with vehicle or BDNF did not promote the axonal regeneration of CN neurons into the PN graft. Application of 2.5 unit/ml chondroitinase ABC resulted in a significant increase (12.8%) in the number of regenerated CN neurons. Double labeling with Fluoro-Gold and NADPH-diaphorase histochemistry showed that the regenerated CN neurons did not express nitric oxide synthase (NOS). Our results suggest that CS is inhibitory to the regeneration of CN neurons following injury of the spinal cord.
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PMID:Chondroitinase ABC promotes axonal regeneration of Clarke's neurons after spinal cord injury. 1079 Aug 83

The effects of removing chondroitin sulfate from chondroitin sulfate proteoglycan molecules on guidance of retinal ganglion cell axons at the optic chiasm were investigated in a brain slice preparation of mouse embryos of embryonic day 13 to 15. Slices were grown for 5 hours and growth of dye-labeled axons was traced through the chiasm. After continuous enzymatic digestion of the chondroitin sulfate proteoglycans with chondroitinase ABC, which removes the glycosaminoglycan chains, navigation of retinal axons was disrupted. At embryonic day 13, before the uncrossed projection forms in normal development, many axons deviated from their normal course, crossing the midline at aberrant positions and invading the ventral diencephalon. In slices from embryonic day 14 embryos, axons that would normally form the uncrossed projection at this stage failed to turn into the ipsilateral optic tract. In embryonic day 15 slices, enzyme treatment caused a reduction of the uncrossed projection that develops at this stage. Growth cones in enzyme-treated slices showed a significant increase in the size both before and after they crossed the midline. This indicates that responses of retinal axons to guidance signals at the chiasm have changed after removal of the chondroitin sulfate epitope. We concluded that the chondroitin sulfate moieties of the proteoglycans are involved in patterning the early phase of axonal growth across the midline and at a later stage controlling the axon divergence at the chiasm.
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PMID:Axon routing at the optic chiasm after enzymatic removal of chondroitin sulfate in mouse embryos. 1082 65

Although the peripheral nerve has the potential to regenerate after injury, degenerative processes may be essential to promote axonal growth into the denervated nerve. One hypothesis is that the nerve contains growth inhibitors that must be neutralized after injury for optimal regeneration. In the present study, we tested whether degradation of chondroitin sulfate proteoglycan, a known inhibitor of axon growth, enhances the growth-promoting properties of grafts prepared from normal donor nerves. Excised segments of rat sciatic nerve were made acellular by freeze-killing before treatment with chondroitinase ABC. Chondroitinase-dependent neoepitope immunolabeling showed that chondroitin sulfate proteoglycan was thoroughly degraded throughout the treated nerve segments. In addition, neuronal cryoculture assays revealed that the neurite-promoting activity of acellular nerves was significantly increased by chondroitinase treatment. Control and chondroitinase-treated acellular nerves were then used as interpositional grafts in a rat nerve injury model. Axonal regeneration into the grafts was assessed 4 and 8 d after implantation by growth-associated protein-43 immunolabeling. At both time points, the number of axons regenerating into acellular grafts treated with chondroitinase was severalfold greater than in control grafts. Growth into the chondroitinase-treated grafts was pronounced after only 4 d, suggesting that the delay of axonal growth normally associated with acellular grafts was attenuated as well. These findings indicate that chondroitinase treatment significantly enhanced the growth-promoting properties of freeze-killed donor nerve grafts. Combined with the low immunogenicity of acellular grafts, the ability to improve axonal penetration into interpositional grafts by preoperative treatment with chondroitinase may be a significant advancement for clinical nerve allografting.
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PMID:Axonal regeneration into acellular nerve grafts is enhanced by degradation of chondroitin sulfate proteoglycan. 1148 43

We analyzed the role of chondroitin sulfate (CS) glycosaminoglycans, putative inhibitors of axonal regeneration in mammals, in the regenerating visual pathway of adult zebrafish. In the adult, CS immunoreactivity was not detectable before or after an optic nerve crush in the optic nerve and tract but was constitutively present in developing and adult nonretinorecipient pretectal brain nuclei, where CSs may form a boundary preventing regenerating optic fibers from growing into these inappropriate locations. Enzymatic removal of CSs by chondroitinase ABC after optic nerve crush significantly increased the number of animals showing erroneous growth of optic axons into the nonretinorecipient magnocellular superficial/posterior pretectal nucleus (83% vs 42% in controls). In vitro, a substrate border of CSs, but not heparan sulfates, strongly repelled regenerating retinal axons from adult zebrafish. We conclude that CSs contribute to repellent axon guidance during regeneration of the optic projection in zebrafish.
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PMID:Repellent guidance of regenerating optic axons by chondroitin sulfate glycosaminoglycans in zebrafish. 1182 14

Our past work indicates that growth-inhibiting chondroitin sulfate proteoglycan (CSPG) is abundant in the peripheral nerve sheaths and interstitium. In this study we tested if degradation of CSPG by chondroitinase enhances axonal regeneration through the site of injury after (a) nerve crush and (b) nerve transection and coaptation. Adult rats received the same injury bilaterally to the sciatic nerves and then chondroitinase ABC was injected near the injury site on one side, and the contralateral nerve was injected with vehicle alone. Nerves were examined 2 days after injury in the nerve crush model and 4 days after injury in the nerve transection model. Chondroitinase-dependent neoepitope immunolabeling showed that CSPG was thoroughly degraded around the injury site in the chondroitinase-treated nerves. Axonal regeneration through the injury site and into the distal nerve was assessed by GAP-43 immunolabeling. Axonal regeneration after crush injury was similar in chondroitinase-treated and control nerves. In contrast, axonal regrowth through the coaptation of transected nerves was markedly accelerated and the ingress of axons into the distal segment was increased severalfold in nerves injected with chondroitinase. On the basis of these results we concluded that growth inhibition by CSPG contributes critically to the poor regenerative growth of axons in nerve transection repair. In addition, degradation of CSPG by injection of chondroitinase ABC at the site of nerve repair increased the ingress of axonal sprouts into basal laminae of the distal nerve segment, presumably by enabling more latitude in growth at the interface of coapted nerve. This suggests that chondroitinase application may be used clinically to improve the outcome of primary peripheral nerve repair.
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PMID:Regeneration of axons after nerve transection repair is enhanced by degradation of chondroitin sulfate proteoglycan. 1209 99

In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity.
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PMID:Reactivation of ocular dominance plasticity in the adult visual cortex. 1242 61

As the preceding discussion has demonstrated, experimental data now indicate that the expression of a number of different CSPGs is increased following CNS injury. The hyalectans neurocan, versican and [figure: see text] brevican, plus NG2 and phosphacan are upregulated following injury and all have been shown to exhibit inhibitory effects on neurite outgrowth in vitro. It is likely therefore that the increased expression of these molecules contributes to the non-permissive nature of the glial scar. The relative contributions of individual molecules remain, however, to be determined. It is important to remember also that not only does the glial scar contain many different inhibitory molecules, but that these are the products of a number of different cells, including not just astrocytes, but also oligodendrocyte progenitor and meningeal cells. It is arguable that the latter two cell types make a greater contribution than astrocytes to the inhibitory environment of the injured CNS. Recently, attempts have been made to alter the CSPG component of the glial scar in the hope that this will facilitate improved axonal regeneration. Three studies (Bradbury et al., 2002; Yick et al., 2000; Moon et al., 2001) have reported an improved regenerative response following treatment of the injured CNS with chondroitinase ABC. CSPGs represent a significant source of inhibition within the injured CNS; these studies indicate that successful CNS regeneration may be brought about by interventions which target these molecules and/or the cells which produce them.
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PMID:Chondroitin sulphate proteoglycans in the CNS injury response. 1244 Mar 75

We have previously demonstrated that enzymatic digestion of chondroitin sulfate proteoglycan (CSPG) at the scar promotes the axonal regrowth of Clarke's nucleus (CN) neurons into an implanted peripheral nerve graft after hemisection of the spinal cord. The present study examined whether degradation of CSPG using chondroitinase ABC promoted the regeneration of CN neurons through the scar into the rostral spinal cord in neonatal and adult rats. Following hemisection of the spinal cord at T11, either vehicle or chondroitinase ABC was applied onto the lesion site. The postoperative survival periods were 2 and 4 weeks. The regenerated CN neurons were retrogradely labeled by Fluoro-Gold injected at spinal cord level C7. In the sham group, there was no regeneration of injured CN neurons in both neonatal and adult rats. Treatment with 2.5 unit/ml chondroitinase ABC in neonates resulted in 11.8 and 8.3% of the injured CN neurons regenerated into the rostral spinal cord at 2 and 4 weeks, respectively. In adults, 9.4 and 12.3%, at 2 and 4 weeks, respectively, of the injured CN neurons regenerated their axons to the rostral spinal cord. The immunoreactivity for the carbohydrate epitope of CSPG was dramatically decreased around the lesion site after treatment with chondroitinase ABC compared to sham control in both neonatal and adult animals. Our results show that axonal regeneration in the spinal cord can be promoted by degradation of CSPG with chondroitinase ABC. This result further suggests that CSPG is inhibitory to the regeneration of neurons in the spinal cord after traumatic injury.
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PMID:Axonal regeneration of Clarke's neurons beyond the spinal cord injury scar after treatment with chondroitinase ABC. 1282 86

Proteoglycans are abundant in the developing brain and there is much circumstantial evidence for their roles in directional neuronal movements such as cell body migration and axonal growth. We have developed an in vitro model of astrocyte cultures of the lateral and medial sectors of the embryonic mouse midbrain, that differ in their ability to support neuritic growth of young midbrain neurons, and we have searched for the role of interactive proteins and proteoglycans in this model. Neurite production in co-cultures reveals that, irrespective of the previous location of neurons in the midbrain, medial astrocytes exert an inhibitory or nonpermissive effect on neuritic growth that is correlated to a higher content of both heparan and chondroitin sulfates (HS and CS). Treatment of astrocytes with chondroitinase ABC revealed a growth-promoting effect of CS on lateral glia but treatment with exogenous CS-4 indicated a U-shaped dose-response curve for CS. In contrast, the growth-inhibitory action of medial astrocytes was reversed by exogenous CS-4. Treatment of astrocytes with heparitinase indicated that the growth-inhibitory action of medial astrocytes may depend heavily on HS by an as yet unknown mechanism. The results are discussed in terms of available knowledge on the binding of HS proteoglycans to interactive proteins, with emphasis on the importance of unraveling the physiological functions of glial glycoconjugates for a better understanding of neuron-glial interactions.
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PMID:Sulfated proteoglycans as modulators of neuronal migration and axonal decussation in the developing midbrain. 1288 53


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