NEUROTROPHIN-3 ENHANCES SPROUTING OF CORTICOSPINAL TRACT DURING DEVELOPMENT AND AFTER ADULT SPINAL-CORD LESION

THE number of neurotrophic factors found in the central nervous system is rapidly growing, but their functions in vivo are largely unknown. In the peripheral nervous system they promote the survival of developi ng and lesioned neurons and enhance nerve fibre growth and regeneratio n1-6. Here we study the effects of nerve growth factor (NGF), brain-de rived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on the larg est tract system leading from the brain to the spinal cord, the cortic ospinal tract (CST)7. The developing CST grows down the spinal cord du ring the first postnatal days and innervates its targets after a waiti ng period by collateral sprouting8-10. We find that NT-3 injected loca lly specifically enhances this sprouting, whereas BDNF has no effect. In adult rats, injection of NT-3 (but not BDNF) into the lesioned spin al cord increases the regenerative sprouting of the transected CST. Th e distance of growth of the sprouts is very restricted, but applicatio n of an antibody that neutralizes myelin-associated neurite growth inh ibitory proteins'' results in long-distance regeneration of CST fibres .