Neuroscience 2005 Abstract
| Presentation Number: | 836.6 |
|---|---|
| Abstract Title: | Chondroitin sulfate proteoglycans that inhibit axon outgrowth can be altered by matrix metalloproteinases. |
| Authors: |
Cua, R. C.*1
; Apte, S. S.2
; Yong, V.1
1Hotchkiss Brain Inst., Univ. of Calgary, Calgary, Canada 2OH, 3330 Hospital Drive NW, T2N 4N1, |
| Primary Theme and Topics |
Development - Transplantation and Regeneration -- Regeneration: CNS |
| Secondary Theme and Topics | Sensory and Motor Systems<br />- Spinal Cord<br />-- Injury and recovery |
| Session: |
836. Regeneration: CNS IV Poster |
| Presentation Time: | Wednesday, November 16, 2005 9:00 AM-10:00 AM |
| Location: | Washington Convention Center - Hall A-C, Board # D57 |
| Keywords: | REGENERATION, NERVE INJURY, EXTRACELLULAR MATRIX, ASTROGLIA |
Acute trauma to the spinal cord in adult mammals can result in permanent loss of function due to scant regeneration of injured axons. The injured axons encounter several barriers to regeneration, one of which is the astroglial scar at the injury site. The astroglial scar contains extracellular matrix (ECM) molecules deposited by reactive astrocytes in response to the injury. It has been shown that one such class of ECM molecules, the chondroitin sulfate proteoglycans (CSPGs), can impede axonal regeneration in vivo as well as inhibit neurite outgrowth in vitro. All CSPGs consist of carbohydrate glycosaminoglycan (GAG) chains attached to a core protein. Chondroitinase ABC, an enzyme that removes the GAG chains, has been shown to facilitate axon regrowth and improve functional recovery in a rat model of spinal cord injury (SCI). However, it has also been found that the core protein can retain inhibitory effects on axon outgrowth. Thus, degrading the core protein of CSPGs, in addition to removing their GAG chains, could enhance axon regrowth and functional recovery after SCI. We hypothesized that CSPG core proteins could be altered by the matrix metalloproteinases (MMPs), which collectively degrade all protein components of the ECM. MMP-2 is upregulated at the injury site after SCI, as is the CSPG neurocan. We tested the proteolytic activity of MMP-2 on neurocan in vitro. Chondroitinase-treated neurocan was incubated with active MMP-2 enzyme at 37°C, and the results were visualized by Western blot with an antibody to neurocan core protein. MMP-2 was found to cleave neurocan in a time-dependent manner. By 24 h, the 180-kDa band of neurocan could not be detected, and this effect was partially inhibited by the MMP inhibitor BB94. We are currently addressing whether alteration by MMP-2 can modify the effect of neurocan on neurite outgrowth in vitro. Our studies may contribute to the successful removal of inhibitory barriers to axonal regrowth in the mammalian CNS.
Supported by Canadian Institutes of Health Research
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2005 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2005. Online.
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