BDNF AND NT-3, BUT NOT NGF, PREVENT AXOTOMY-INDUCED DEATH OF RAT CORTICOSPINAL NEURONS IN-VIVO

Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) hav e been identified as survival factors for adult axotomized rat cortico spinal neurons (CSN) in vivo. Axotomy of corticospinal neurons at the level of the internal capsule induced death of 46% of the CSN within t he first week after axotomy. The surviving population of CSN displayed severe atrophy with mean cross-sectional area 49% of their unlesioned contralateral counterparts 7 days after axotomy. Using in situ hybrid ization to assess the expression of the receptors for the family of ne urotrophins, we found trkB and trkC but not trkA mRNA expression in CS N. Intraparenchymal application of BDNF or NT-3 at doses of 12 mu g/da y for 7 days via an osmotic minipump fully prevented the axotomy-induc ed death of CSN. Interestingly, no neuronal atrophy was seen after BDN F application while NT-3 had only a partial effect on the size of the axotomized CSN. Nerve growth factor did not prevent death or cell atro phy, consistent with the lack of trkA mRNA expression in these neurons . These findings show that BDNF and NT-3 are survival factors for adul t rat CSN in vivo, and may contribute to the development of therapeuti c strategies aiming at the prevention of CSN degeneration in human mot or neuron diseases.