Influence of the axotomy to cell body distance in rat rubrospinal and spinal motoneurons: Differential regulation of GAP-43, tubulins, and neurofilament-M

Axotomized motoneurons regenerate their axons regardless of whether axotomy occurs proximally or distally from their cell bodies. In contrast, regener ation of rubrospinal axons into peripheral nerve grafts has been detected a fter cervical but not after thoracic injury of the rubrospinal tract. By us ing in situ hybridization (ISH) combined with reliable retrograde tracing m ethods, we compared regeneration-associated gene expression after proximal and distal axotomy in spinal motoneurons versus rubrospinal neurons. Regard less of whether they were axotomized at the iliac crest (proximal) or popli teal fossa (distal), sciatic motoneurons underwent highly pronounced change s in ISH signals for Growth Associated Protein 43 (GAP-43) (10-20x increase ) and neurofilament M (60-85% decrease). In contrast, tubulin ISH signals s ubstantially increased only after proximal axotomy (3-5x increase). To comp are these changes in gene expression with those of axotomized rubrospinal n eurons, the rubrospinal tract was transected at the cervical (proximal) or thoracic (distal) levels of the spinal cord. Cervically axotomized rubrospi nal neurons showed three- to fivefold increases in ISH signals for GAP-43 a nd tubulins (only transient) and a 75% decrease for neurofilament-M. In sha rp contrast, thoracic axotomy had only marginal effects. After implantation of peripheral nerve transplants into the spinal cord injury sites, retrogr ade labeling with the sensitive retrograde tracer Fluoro-Gold identified re generating rubrospinal neurons only after cervical axotomy. Furthermore, ru brospinal neurons specifically regenerating into the transplants were hyper trophied and expressed high levels of GAP-43 and tubulins. Taken together, these data support the concept that, even if central nervous system (CNS) a xons are presented with a permissive/supportive environment, appropriate ce ll body responses to injury are a prerequisite for CNS axonal regeneration. (C) 1999 Wiley Liss, Inc.