Role of chondroitin sulfate proteoglycans (CSPGs) in synaptic plasticity and neurotransmission in mammalian spinal cord.

Arsen Hunanyan,Guillermo Garcia-Alias,Lorne Mendell,Joel Levine,James Fawcett,Victor Arvanian

doi:10.1038/npre.2009.3681.1

Abstract

AbstractChronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX. Intraspinal injections of Chondroitinase-ABC, known to digest chondroitin sulfate proteoglycans (CSPGs) in the vicinity of injury, prevented this decline of axonal conduction. This was associated with improved locomotor function. We further injected three purified CSPGs into the lateral column of the uninjured cord at T10: NG2 and neurocan, which increase in the vicinity of a spinal injury, and aggrecan, which decreases. Intraspinal injection of NG2 acutely depressed axonal conduction through the injection region in a dose dependent manner. Similar injections of saline, aggrecan, or neurocan had no significant effect. These results identify a novel acute action of CSPGs on axonal conduction in spinal cord, and suggest that antagonism of proteoglycans reverses or prevents the decline of axonal conduction, in addition to stimulating axonal growth.

Highlights

Chronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX
Our results demonstrate that the post-injury conduction block in axons close to the lesion can be prevented by Ch’ase infusion, and that NG2, one of the chondroitin sulfate proteoglycans (CSPGs) upregulated after injury, can block axonal conduction and transmission to motoneurons
In rats tested initially on one side with aggrecan with no decline in conduction observed, subsequent injections of NG2 in the contralateral white matter depressed the evoked responses on that side (Fig. 5 c, d; n = 3). These results suggest that the depression of axonal conduction is specific to NG2, but not other CSPGs studied, i.e. aggrecan or neurocan

Summary

Introduction

Chronic unilateral hemisection (HX) of the adult rat spinal cord diminishes conduction through intact fibers in the ventrolateral funiculus (VLF) contralateral to HX. Intraspinal injections of Chondroitinase-ABC, known to digest chondroitin sulfate proteoglycans (CSPGs) in the vicinity of injury, prevented this decline of axonal conduction. We found that a lateral hemisection lesion (HX) of the adult rat spinal cord induces failure of axonal conduction through the intact axons contralateral to the HX, beginning 1 week after injury and persisting for at least 14 weeks [20] The initiation of these physiological deficits coincided with the time that the elevated level of CSPGs in tissue surrounding the HX reached its peak [21]. Set 1 was directed towards evaluation of the ability of CSPG degradation to restore axonal conduction that normally declines contralateral to hemisection These rats received a HX at thoracic T10 level; followed by immediate perilesional intraspinal injection of Ch’ase, or the neutral bacterial enzyme penicillinase (P’ase) as control. Some of these results have been reported in abstract form [23]

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Conclusion