ausblenden:
Schlagwörter:
CHONDROITIN SULFATE PROTEOGLYCANS; ROOT GANGLION NEURONS; NEURITE
OUTGROWTH; TENASCIN-C; CELL-ADHESION; DEVELOPMENTAL REGULATION;
ALPHA-7-BETA-1 INTEGRIN; NERVOUS-SYSTEM; CNS AXONS; NOGO-Aadeno-associated virus; alpha9 integrin; axon regeneration; dorsal root
ganglion; kindlin-1; spinal cord;
Zusammenfassung:
After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth of axons if they express a tenascin-binding integrin, particularly alpha 9 beta 1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a beta 1-binding integrin activator, kindlin-1. We examined the synergistic effect of alpha 9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of alpha 9 integrin or kindlin-1 alone promoted much less regeneration and recovery.
