The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces

In the dorsal root entry zone (DREZ) peripheral sensory axons fail to regenerate past the peripheral nervous system/central nervous system (PNS/CNS) interface. Additionally, in the spinal cord, central fibers that regenerate into Schwann cell (SC) bridges can enter but do not exit at the distal Schwann cell/astrocyte (AC) boundary. At both interfaces where limited mixing of the two cell types occurs, one can observe an up-regulation of inhibitory chondroitin sulfate proteoglycans (CSPGs). We treated confrontation Schwann cell/astrocyte cultures with the following: (1) a deoxyribonucleic acid (DNA) enzyme against the glycosaminoglycan (GAG)-chain-initiating enzyme, xylosyltransferase-1 (XT-1), (2) a control DNA enzyme, and (3) chondroitinase ABC (Ch'ase ABC) to degrade the GAG chains. Both techniques for reducing CSPGs allowed Schwann cells to penetrate deeply into the territory of the astrocytes. After adding sensory neurons to the assay, the axons showed different growth behaviors depending upon the glial cell type that they first encountered during regeneration. Our results help to explain why regeneration fails at PNS/CNS glial boundaries.