University of Kentucky

Can Sensory Neurons Produce Their Own An Anti-Inhibitory Factor To Promote Regeneration?

Institution

University of Kentucky

Abstract

Following spinal cord injury (SCI), chondroitin sulfate proteoglycans (CSPGs) are up-regulated by reactive astrocytes of the glial scar, leading to failed regeneration and a subsequent loss of motor and/or sensory function. CSPGs consist of a protein core to which glycosaminoglycans (sugar chains) are covalently attached, and represent a large, extracellular matrix barrier to neuronal regeneration. Previous data from our laboratory has shown sensory neuron outgrowth is density dependent. Extrapolating from this observation, we asked, “Might a group of sensory neurons be able to lure other neurons through a region consisting of inhibitory CSPGs?” To test this hypothesis, sensory neurons were cultured (on laminin) on either one side, or both sides, of a strip of adsorbed CSPG (150 ug/ml; 48 hrs). Images were taken of the regions of outgrowth and the CSPG stripe. Neurons were identified with anti-neuron specific beta-III tubulin, and the CSPG stripe was identified using an anti-CSPG antibody. A Merz grid was used to quantify outgrowth under each condition. Results of this study showed that when neurons were plated on only one side of the inhibitory CSPG stripe, the neuronal processes grew to the edge of the CSPG border and turned, i.e. they were inhibited, mimicking the behavior they exhibit at the CSPG-producing glial scar in vivo following SCI. However, when sensory neurons were grown on BOTH sides of the CSPG stripe, there was significant outgrowth ACROSS the typically inhibitory CSPG, and toward the adjacent group of sensory neurons. This preliminary data suggests that sensory neurons may secrete a factor(s) that promote their own elongation, and that potentially, strategic placement of such factors may be used to overcome CSPG inhibition and promote regeneration. [Support: NIH/NINDS NS053470 to DMS and TMH; *faculty mentor].

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Can Sensory Neurons Produce Their Own An Anti-Inhibitory Factor To Promote Regeneration?

Following spinal cord injury (SCI), chondroitin sulfate proteoglycans (CSPGs) are up-regulated by reactive astrocytes of the glial scar, leading to failed regeneration and a subsequent loss of motor and/or sensory function. CSPGs consist of a protein core to which glycosaminoglycans (sugar chains) are covalently attached, and represent a large, extracellular matrix barrier to neuronal regeneration. Previous data from our laboratory has shown sensory neuron outgrowth is density dependent. Extrapolating from this observation, we asked, “Might a group of sensory neurons be able to lure other neurons through a region consisting of inhibitory CSPGs?” To test this hypothesis, sensory neurons were cultured (on laminin) on either one side, or both sides, of a strip of adsorbed CSPG (150 ug/ml; 48 hrs). Images were taken of the regions of outgrowth and the CSPG stripe. Neurons were identified with anti-neuron specific beta-III tubulin, and the CSPG stripe was identified using an anti-CSPG antibody. A Merz grid was used to quantify outgrowth under each condition. Results of this study showed that when neurons were plated on only one side of the inhibitory CSPG stripe, the neuronal processes grew to the edge of the CSPG border and turned, i.e. they were inhibited, mimicking the behavior they exhibit at the CSPG-producing glial scar in vivo following SCI. However, when sensory neurons were grown on BOTH sides of the CSPG stripe, there was significant outgrowth ACROSS the typically inhibitory CSPG, and toward the adjacent group of sensory neurons. This preliminary data suggests that sensory neurons may secrete a factor(s) that promote their own elongation, and that potentially, strategic placement of such factors may be used to overcome CSPG inhibition and promote regeneration. [Support: NIH/NINDS NS053470 to DMS and TMH; *faculty mentor].