Neuroscience 2003 Abstract
| Presentation Number: | 880.1 |
|---|---|
| Abstract Title: | Immature astrocytes: getting rid of the glial scar and promoting axon regeneration. |
| Authors: |
Miller, J. H.*1
; Tom, V. J.1
; Doller, C. M.1
; Silver, J.1
1Deptartment of Neurosci., Case Western Reserve Univ. Sch. of Med., Cleveland, OH |
| Primary Theme and Topics |
Development - Transplantation and Regeneration -- Regeneration: CNS |
| Session: |
880. CNS Regeneration Slide |
| Presentation Time: | Wednesday, November 12, 2003 1:00 PM-1:00 PM |
| Location: | Morial Convention Center - Room 391 |
| Keywords: | PROTEOGLYCAN, INHIBITION, SENSORY NEURONS, SPINAL CORD INJURY |
CNS injury results in the formation of a glial scar consisting of reactive astrocytes, microglia, fibroblasts, and growth inhibitory proteoglycans (PG) that prevent regeneration. However, the CNS of immature animals is capable of regeneration following injury, in part because reactive gliosis is growth promoting rather than inhibitory and the glial scar does not form. This work seeks to elucidate why that difference arises by examining immature astrocytes (IA, <8 DIV) and mature astrocytes (MA, >35 DIV) on an inhibitory gradient of the PG, aggrecan, along with the growth promoting molecule, laminin. No type of mature cell, either neuron or glia, can penetrate the outermost rim in this highly inhibitory model of the scar. We have learned that IA are capable of enhanced growth, as compared to MA, on the aggrecan gradient. The IA display a more stellate, expanded morphology, while the MA assume a banded, compacted morphology similar to that in the glial scar. Additionally, IA are capable of digesting aggrecan with greater efficacy than MA, possibly with membrane bound MMP-2 and 9, providing a more favorable substrate for growth. Pre-treatment with Chondroitinase ABC (ChABC) enhances the growth of both IA and MA by removal of the GAG chain of aggrecan, but only immature cells can bridge the outer rim. The addition of adult sensory neurons onto cultures of astrocytes already growing on the gradient results in the enhanced growth of sensory axons across the most inhibitory part of the gradient, using those astrocytes that cross the outer rim as a bridge. The behavior of IA and MA on an inhibitory growth substrate models their behavior in the animal following injury. Additionally, the enhanced growth of IA, as well as the growth promoting effects the astrocytes have on sensory neurons, makes young cells, in combination with ChABC, attractive as a strategy to treat SCI.
Supported by NS25713, Daniel Heumann Fund
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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